Dissertations / Theses: 'In vivo electrophysiology recording'

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Annecchino, Luca. "Development and validation of a robotic two-photon targeted whole-cell recording system for in vivo electrophysiology." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/56991.

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Understanding the functional principles of the mammalian cortical circuit is a major challenge in neuroscience. To make progress towards this understanding, one needs to be able to assess the behavioural dynamics of individual neuronal elements of this circuit. Manual whole-cell recording (WCR) in vivo is recognised as the “gold standard” method for electrophysiological interrogation of individual neurons. It allows subthreshold and suprathreshold signals to be recorded, perturbations to be applied through current injection, and DNA vectors to be directly delivered into the patched cells as part of the pipette internal solution. Unfortunately, the WCR technique for in vivo application is a “blind” procedure and has a low-throughput. In addition, the genetic and morphological identity of the recorded neuron often cannot be accounted for. The inherent cell-type non selectivity of this technique can be overcome by combining WCR with two-photon laser scanning microscopy, and targeting recordings to specifically labelled individual cells or cell classes. Targeted electrophysiological interrogation allows one to examine the properties of both single cells and neuronal assemblies and, additionally, the role of cell type-specific proteins in orchestrating neuronal responses. Targeted recordings in vivo may enable to test a wide range of hypotheses related to information processing in the cortical circuits. However, probing and studying the properties of individual cells in live animal preparations remains a challenge in neuroscience. In particular, precise vision-guided control of patch pipette motion and viewpoint generation of microscope objective for targeted single-cell electrophysiological interrogation is problematic. It requires specialised skills acquired through extensive practice and training by individual operators. Although automatic patch clamp technology has been in use for some years exclusively for cell culture-based paradigms, only recently has Kodandaramaiah et al. demonstrated a “blind” automated patch clamp system for in vivo recordings. However, a fully automatic method for in vivo WCR targeting specific cells or cell-types has not been implemented in any robotic system so far. In this study an automated two-photon targeted whole-cell patch clamping algorithm is demonstrated as a workable solution. The aim of this work was to develop a robotic integrated targeted autopatcher that minimised labour intensive procedures and increased the throughput both in blind and two-photon targeted WCR in live animals. The system automatically controls a micromanipulator, a microelectrode signal amplifier a two-photon microscope and a custom made regulator for controlling the internal pressure of the pipette. The two-photon microscope acquires images of fluorescently labelled cells, and cell-targets for patch clamp are selected via a point-and-click graphical user interface. Optical coordinates are initially converted to the micromanipulator coordinate system and a suitable path calculated to guide the patch pipette towards the target. This platform allows to compensate for brain tissue deformation and subsequent neuronal target movement caused by pipette insertion. As proof-of-concept, the system was tested in both “blind” and two-photon targeted paradigms and achieved performances comparable to human operators, in terms of yield, recording quality and operational speed. Hit rate for “blind” WCR was 51.4% (n=18, 35 attempts across 5 mice). RITA was also calibrated and tested for targeting specific cell types in the cortex of intact mouse brain labelled via fluorescent dye loading (e.g. Oregon Green BAPTA-1 and/or Sulforhodamine 101). Pipettes were automatically guided to the target cells and recordings obtained from visually identified neurons as well as astrocytes. These results prove the feasibility of robotic targeted WCR patch clamp in vivo and establish this system as a powerful tool for automated electrophysiological experiments in the brain.

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Lau, Petrina Yau Pok. "Long-term plasticity of excitatory inputs onto identified hippocampal neurons in the anaesthetized rat." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:172e0d36-0d67-4932-962e-9ee08dcc366c.

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Use-dependent long-term plasticity in synaptic connections represents the cellular substrate for learning and memory. The hippocampus is the most thoroughly investigated brain area for long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) are both well characterized in glutamatergic excitatory connections between hippocampal principal cells in vitro and in vivo. An increasing number of studies based on acute brain slice preparations report LTP and LTD in excitatory synapses onto postsynaptic hippocampal GABAergic inhibitory interneurons. However, a systematic study of activity-induced long-term plasticity in excitatory synaptic connections to inhibitory GABAergic interneurons in vivo is missing. To determine whether LTP and LTD occur in excitatory synaptic connections to the hippocampal CA1 area GABAergic interneurons types in intact brain, I have used juxtacellular recording to measure synaptically evoked short-delay postsynaptic action potential probability in identified CA1 neurons in the urethane-anaesthetized rats. Plasticity in excitatory synaptic connections to CA1 cell types was measured as a change of afferent pathway stimulation-evoked postsynaptic spike probability and delay. In the study only experiments with monosynaptic-like short-delay (range 3-12 ms) postsynaptic spikes phase-locked to afferent stimulation were used. Afferent fibres were stimulated from the CA1 area of the hippocampus at the contralateral (left) side to avoid simultaneous monosynaptic activation of GABAergic fibres and to exclude antidromic spikes in recorded CA1 cells (in right hemisphere). Plasticity in pathways was tested using theta-burst high-frequency stimulation (TBS, 100 pulses), which is one of the most common synaptic plasticity induction protocols in acute brain slice studies. I discovered that TBS elicited permanent potentiation in single shock-evoked postsynaptic spike probability with shortening or no change in evoked spike latency in various postsynaptic neuron types including three identified pyramidal cells and parvalbumin-expressing (PV+) interneurons. Most fast-spiking PV+ cells showed LTP including an axo-axonic cell and one bistratified cell, whereas two identified basket cells exhibited LTD in similar experimental conditions. In addition, I discovered diverse plasticity in non-fast spiking interneurons, reporting LTP in an ivy cell, and LTD in three incompletely identified regular-spiking CA1 interneurons. I report that the underlying brain state, defined as theta oscillation (3-6 Hz) or non-theta in local field potential, failed to explain whether LTP, LTD or no plasticity was generated in interneurons. The results show that activity-induced potentiation and depression similar to LTP and LTD also occur in excitatory synaptic pathways to various CA1 interneurons types in vivo. I propose that long-term plasticity in excitatory connections to inhibitory interneurons may be take place in learning and memory processes in the hippocampus.

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Chaudun, Fabrice. "Involvement of dorsomedial prefrontal projections pathways to the basolateral amygdala and ventrolateral periaqueductal grey matter in conditioned fear expression." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0118/document.

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A l’heure actuelle, une des principales questions des neurosciences comportementales est de comprendre les bases neurales des apprentissages et de comprendre comment des modifications au sein de circuits neuronaux spécifiques contrôlent les changements comportementaux liés à une expérience particulière. De nombreuses études ont récemment mis en évidence le rôle important des circuits neuronaux dans les phénomènes d’apprentissages associatifs, et notamment dans la régulation des comportements de peur. Cependant, leurs caractéristiques anatomiques et fonctionnelles restent encore largement inconnues. L’une des principales fonctions des circuits neuronaux est leur capacité à adapter le comportement en fonction de la nature des informations internes ou environnementales disponibles. Malgré de nombreux progrès réalisés sur la compréhension des substrats et mécanismes neuronaux sous tendant le conditionnement de peur au sein de structures telles que l'amygdale (AMG), le cortex préfrontal dorso-médian (dmPFC) et la substance grise periaqueducale (PAG), les mécanismes neuronaux gouvernant les interactions inter-structure ainsi que le contrôle local de ces différents circuits neuronaux restent encore largement inconnus. Dans ce contexte, ce travail de thèse a eupour objectifs principaux, d’évaluer la contribution des voies de projections dmPFC-BLA et dmPFC-vlPAG dans la régulation des comportements de peur, et, d’identifier les mécanismes neuronaux sous-jacent contrôlant l'expression de la peur. Afin de répondre à ces questions, nous avons utilisé conjointement des enregistrements électrophysiologiques unitaires et de potentiels de champs couplés à des approches optogénétiques au cours de l’expression de la peur conditionnée. Nous avons pu mettre en évidence un nouveau mécanisme neuronal basé sur une oscillation cérébrale à 4 Hz entre le dmPFC et le BLA impliqué dans la synchronisation neuronale des neurones de ces deux structures nécessaire à l’expression de la peur. Nous avons aussi démontré que le dmPFC via ses projections sur le vlPAG contrôle directement l’expression de la peur. Ensemble, nos données contribuent à une meilleure compréhension des circuits neuronaux ainsi que des mécanismes du comportement de peur qui dans le futur pourront aider à une amélioration thérapeutique des troubles anxieux
A central endeavour of modern neuroscience is to understand the neural basis of learningand how the selection of dedicated circuits modulates experience-dependent changes inbehaviour. Decades of research allowed a global understanding of the computations occurring inhard-wired networks during associative learning, in particular fear behaviour. However, brainfunctions are not only derived from hard-wired circuits, but also depend on modulation of circuitfunction. It is therefore realistic to consider that brain areas contain multiple potential circuitswhich selection is based on environmental context and internal state. Whereas the role of entirebrain areas such as the amygdala (AMG), the dorsal medial prefrontal cortex (dmPFC) or theperiaqueductal grey matter (PAG) in fear behaviour is reasonably well understood at themolecular and synaptic levels, there is a big gap in our knowledge of how fear behaviour iscontrolled at the level of defined circuits within these brain areas. More particularly, whereas thedmPFC densely project to both the basolateral amygdala (BLA) and PAG, the contributions ofthese two projections pathway during fear behaviour are largely unknown. Beside theinvolvement of these neuronal pathways in the transmission of fear related-information, theneuronal mechanisms involved in the encoding of fear behaviour within these pathways are alsovirtually unknown. In this context, the present thesis work had two main objectives. First,evaluate the contribution of the dmPFC-BLA and dmPFC-vlPAG pathways in the regulation offear behaviour, and second, identify the neuronal mechanisms controlling fear expression in thesecircuits. To achieve these goals, we used a combination of single unit and local field potentialrecordings coupled to optogenetic approaches in behaving animals submitted to a discriminativefear conditioning paradigm. Our results first, identified a novel neuronal mechanism of fear expression based on the development of 4 H oscillations within dmPFC-BLA circuits thatdetermine the dynamics of freezing behaviour and allows the long-range synchronization offiring activities to drive fear behaviour. Secondly, our results identified the precise circuitry at thelevel of the dmPFC and vlPAG that causally regulate fear behaviour. Together these data provideimportant insights into the neuronal circuits and mechanisms of fear behaviour. Ultimately thesefindings will eventually lead to a refinement of actual therapeutic strategies for pathological conditions such as anxiety disorders

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Pye, Richard Laurence. "Measuring the Acute Physiological Effects of Leptin in the Carotid Body." Wright State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1449583350.

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Bernstein, Jacob (Jacob Gold). "Development of extracellular electrophysiology methods for scalable neural recording." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107581.

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Thesis: Ph. D., Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references.
In order to map the dynamics of neural circuits in mammalian brains, there is a need for tools that can record activity over large volumes of tissue and correctly attribute the recorded signals to the individual neurons that generated them. High-resolution neural activity maps will be critical for the discovery of new principles of neural coding and neural computation, and to test computational models of neural circuits. Extracellular electrophysiology is a neural recording method that has been developed to record from large populations of neurons, but well-known problems with signal attribution pose an existential threat to the viability of further system scaling, as analyses of network function become more sensitive to errors in attribution. A key insight is that blind-source separation algorithms such as Independent Component Analysis may ameliorate problems with signal attribution. These algorithms require recording signals at much finer spatial resolutions than existing probes have accomplished, which places demands on recording system bandwidth. We present several advances to technologies in neural recording systems, and a complete neural recording system designed to investigate the challenges of scaling electrophysiology to whole brain recording. We have developed close-packed microelectrode arrays with the highest density of recording sites yet achieved, for which we built our own data acquisition hardware, developed with a computational architecture specifically designed to scale to over several orders of magnitude. We also present results from validation experiments using colocalized patch clamp recording to obtain ground-truth activity data. This dataset provides immediate insight into the nature of electrophysiological signals and the interpretation of data collected from any electrophysiology recording system. This data is also essential in order to optimize probe development and data analysis algorithms which will one day enable whole-brain activity mapping.
by Jacob G. Bernstein.
Ph. D.

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Silpa, Nagari. "NANOSTRUCTURED SENSORS FOR IN-VIVO NEUROCHEMICAL RECORDING." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_theses/487.

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L-glutamate plays a vital role in central nervous system. It is a neurotransmitterassociated with several neurological disorders like Parkinson's disease, epilepsyand stroke. Continuous and fast monitoring of this neurotransmitter has become amajor concern for neuroscientists throughout the world. A simple, sensitive, and reliable L-glutamate microsensor with short responsetime has been developed using ceramic-based microelectrode arrays with platinum recording sites. The electrodes were modified by electrodeposition of Platinum black (Pt-black) to detect hydrogen peroxide (H2O2) which was produced by enzymatic reactions of glutamate oxidase immobilized on the electrode surface. Modification of Pt electrodes with Pt-black has been adoptedbecause the microscale roughness of Pt-black increases the effective surface area of the electrode and promotes efficiency of H2O2 electro-oxidation. The modified Pt recording sites were coated with m-phenylenediamine (mPD) and L-glutamate oxidase (L-GluOx). mPD acts as an barrier for extracellular interferents such as ascorbic acid and dopamine, thus increasing the selectivity of electrode for Glutamate (Glu). This modified microsensor was highly sensitive to H2O2(686.3??156.48 ??AmM-1cm-2), and Glutamate (492.2??112.67 ??AmM-1cm-2) at 700mV versus Ag/AgCl reference. Deposition of Pt nano-particles on recording sites enhanced the sensitivity to H2O2 by 2 times and the sensitivity to glutamate by 1.5 times.

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Nagari, Silpa. "Nano-structured sensors for in-vivo neurochemical recording." Lexington, Ky. : [University of Kentucky Libraries], 2007. http://hdl.handle.net/10225/735.

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Thesis (M.S.)--University of Kentucky, 2007.
Title from document title page (viewed on March 24, 2008). Document formatted into pages; contains: ix, 55 p. : ill. (some col.). Includes abstract and vita. Includes bibliographical references (p. 53-54).

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Dodds, Catherine Jane. "The action of naturally-occuring semiochemicals on feeding behaviour and neurophysiology of the field slug Deroceras reticulatum (Mueller)." Thesis, University of Portsmouth, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310443.

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Hasegawa, Taku. "A wireless system with a motorized microdrive for neural recording in freely behaving animals." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/199467.

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Kodandaramaiah, Suhasa Bangalore. "Robotics for in vivo whole cell patch clamping." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/51932.

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Whole-cell patch clamp electrophysiology of neurons in vivo enables the recording of electrical events in cells with great precision, and supports a wide diversity of morphological and molecular analysis experiments important for the understanding of single-cell and network functions in the intact brain. However, high levels of skill are required in order to perform in vivo patching, and the process is time-consuming and painstaking. Robotic systems for in vivo patching would not only empower a great number of neuroscientists to perform such experiments, but would also open up fundamentally new kinds of experiment enabled by the resultant high throughput and scalability. We discovered that in vivo blind whole cell patch clamp electrophysiology could be implemented as a straightforward algorithm and developed an automated robotic system that was capable of performing this algorithm. We validated the performance of the robot in both the cortex and hippocampus of anesthetized mice. The robot achieves yields, cell recording qualities, and operational speeds that are comparable to, or exceed, those of experienced human investigators. Building upon this framework, we developed a multichannel version of “autopatcher” robot capable establishing whole cell patch clamp recordings from pairs and triplets of neurons in the cortex simultaneously. These algorithms can be generalized to control arbitrarily large number of electrodes and the high yield, throughput and automation of complex set of tasks results in a practical solution for conducting patch clamp recordings in potentially dozens of interconnected neurons in vivo.

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Crnic, Agnes. "Effects of Acute and Sustained Administration of Vilazodone (EMD68843) on Monoaminergic Systems: An In Vivo Electrophysiological Study." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31498.

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Vilazodone is a partial 5-HT1A receptor agonist and a selective serotonin reuptake inhibitor (SSRI). Acute administration caused a dose-dependent decrease in dorsal raphe (DR) serotonin (5-HT) neuron firing rates. Vilazodone significantly decreased DR 5-HT neuronal firing following 2-day administration, which was shown to recover completely after 14-day administration. The 2-day administration of vilazodone significantly decreased firing in ventral tegmental area dopamine neurons; this effect persisted after 14-day treatment. The firing rate of norepinephrine neurons in the locus coeruleus was not significantly altered following 2-day treatment but did decrease following 14-day treatment. In the hippocampus, 14-day treatment with vilazodone significantly enhanced tonic activation, while having no effect on 5-HT reuptake. Vilazodone produced effects similar to conventional SSRIs while also inducing alterations in monoaminergic neurons that may be associated with its 5-HT1A properties and may have a role in the field of treatment resistant depression.

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Suk, Ho-Jun. "Automated cell-targeted electrophysiology in vivo and non-invasive gamma frequency entrainment." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122429.

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Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 105-110).
Targeted patch clamp recording is a powerful method for characterizing visually identified cells in intact neural circuits, but it requires skill to perform. We found that a closed-loop real-time imaging strategy, which continuously compensates for cell movement while approaching the cell with a pipette tip, allows for the development of an algorithm amenable to automation. We built a robotic system that can implement this algorithm and validated that our system can automatically patch fluorophore-expressing neurons of multiple types in the living mouse cortex, with yields comparable to skilled human experimenters. By facilitating targeted patch clamp recordings in vivo, our robot may enable scalable characterization of identified cell types in intact neural circuits. Activities of individual neurons in neural circuits give rise to network oscillations, whose frequencies are closely related to specific brain states.
For example, network oscillations in the 30 - 90 Hz range, observed using electroencephalogram (EEG), are called gamma oscillations and increase during attention, memory formation, and recall. In Alzheimer's disease (AD), gamma oscillations are disrupted compared to healthy individuals. Recently, noninvasive visual and auditory stimulations at 40 Hz, called Gamma ENtrainment Using Sensory stimulus ("GENUS"), have been shown to positively impact pathology and improve memory in AD mouse models, with concurrent visual and auditory GENUS leading to a more widespread effect in the AD mouse brain compared to visual or auditory stimulation alone. However, it is unclear what effect such sensory stimulations would have on the human brain. To test for the safety and feasibility of GENUS in humans, we developed a device that can deliver 40 Hz light and sound stimulations at intensity levels tolerable to humans.
We found that our device can safely lead to steady 40 Hz entrainment in cognitively normal young (20 - 33 years old) and older (55 - 75 years old) subjects, with concurrent visual and auditory stimulation leading to stronger and more widespread entrainment than visual or auditory stimulation alone. These findings suggest that GENUS can be a safe and effective method for widespread 40 Hz entrainment, which may have therapeutic effects in people suffering from AD.
by Ho-Jun Suk.
Ph. D.
Ph.D. Harvard-MIT Program in Health Sciences and Technology

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Parent, Katherine L., and Katherine L. Parent. "Probing Neural Communication by Expanding In Vivo Electrochemical and Electrophysiological Measurements." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/626155.

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Neural communication is imperative for physical and mental health. Dysfunction in either ionic signaling or chemical neurotransmission can cause debilitating disorders. Thus, study of neurotransmission is critical not only to answer important fundamental questions regarding learning, decision making, and behavior but also to gain information that can provide insight into the neurochemistry of neurological disorders and lead to improved treatments. The work presented herein describes the development of techniques and instrumentation to enable advancements in neuroscientific inquiry. The effect of different temporal patterns and durations of simulation of the prefrontal cortex on dopamine release in the nucleus accumbens was examined and revealed a complex interaction that can help improve deep brain stimulation therapies. A measurement platform that combines electrophysiological and electrochemical techniques is described. The instrumentation is capable of concurrent monitoring of neural activity and dopamine release in vivo and in freely moving rodents. Analysis techniques to allow absolute quantification of tonic dopamine concentrations in vivo are detailed and the temporal resolution of the technique was vastly improved from ten minutes to forty seconds. An instrument that can simultaneously probe both dopamine and serotonin dynamics in either of their two temporal modes of signaling (tonic and phasic) using either fast-scan cyclic voltammetry or fast-scan controlled-adsorption voltammetry at two individually addressable microelectrodes is described. Together these new tools represent a significant step forward in the field of neuroanalytical chemistry by enable multiple brain regions, signaling modes (ionic flux in addition to both tonic and phasic neurotransmission), neurochemicals, and to be measured together.

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Pitcher, Toni Leigh, and n/a. "In vivo electrophysiology of striatal spiny projection neurons in the spontaneously hypertensive rat (SHR)." University of Otago. Department of Anatomy & Structural Biology, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070321.114819.

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The aim of this thesis was to investigate neuronal cellular mechanisms that may underlie the behavioural characteristics of the spontaneously hypertensive rat strain (SHR). The SHR was developed by selective breeding for elevated blood pressure and is also described as having increased levels of locomotor behaviour compared to its normotensive control strain, the Wistar-Kyoto. This hyperactivity and other behaviours, including altered sensitivity to reinforcement, have been used to model aspects of behaviour displayed in attention deficit hyperactivity disorder. In vivo intracellular recording of striatal spiny projection neuron activity in urethaneanaesthetised animals from three genetically related strains: the SHR, Wistar-Kyoto and standard Wistar, was employed to measure basic cellular properties and cellular mechanisms of reward-related learning. This population of neurons was chosen because alterations in their activity can influence behaviour and they are known to show cellular changes (synaptic plasticity) that are associated with learning. Cellular properties were measured in 71 neurons. Comparison between strains revealed a significant difference in action potential amplitude and duration between the SHR and Wistar-Kyoto strains. Interestingly, when measured at a later time, in a different sample of rats, the SUR action potential amplitude and duration were significantly different from the earlier sample. A change in the membrane potential repolarisation rate following action potential firing also occurred over this time. Twenty-nine of these neurons were also used in a study investigating the neuronal responses to a low dose of amphetamine (0.5 mg/kg). Changes were observed in some cellular properties following intraperitoneal administration of amphetamine. Synaptic plasticity at the corticostriatal synapses is sensitive to the timing of dopamine release in relation to cortical input. In anaesthetised preparations the spiny projection neuron membrane potential fluctuates between hyperpolarised (DOWN) and depolarised (UP) states, which reflect the level of cortical input. During the present study the responses of nine neurons to the induction of cortical spreading depression were observed to investigate the suitability of this method for use during synaptic plasticity experiments. Spiny projection neurons showed unpredictable responses to cortical spreading depression, therefore this method was not used further. Corticostriatal synaptic plasticity was induced in sixteen spiny projection neurons from two strains: SHR and Wistar. High frequency stimulation of the dopamine neurons in the substantia nigra, during the DOWN-state, did not induce any significant changes in corticostriatal synaptic efficacy. This was also true when high frequency stimulation of dopamine neurons was applied during the UP-state in neurons from the SHR strain. This thesis represents the first in vivo intracellular study of neuronal physiology in the SHR and Wistar-Kyoto rat strains. Results revealed action potential differences between these two behaviourally distinct rat strains. Synaptic mechanisms thought to underlie reward-related learning were not different between the SHR and Wistar strains, although the observed levels of plasticity were inconsistent with previous literature.

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Geddes, Sean D. "Dynamic Regulation of Synaptic Transmission onto Serotonin Neurons by Antidepressants." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23532.

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Antidepressants are generally believed to exert their clinical efficacy by enhancing 5-HT transmission. Interestingly, sustained administration of selective serotonin (5-HT) reuptake inhibitors (SSRIs) strongly suppresses in the first few days the firing activity of 5-HT neurons in the dorsal raphe nucleus (DRN), thereby severely hampering the increase of 5-HT in target regions. Remarkably, the firing activity of 5-HT neurons gradually recovers over the time course of treatment and this recovery is believed to be accounted for by the desensitization of 5-HT1A somatodendritic autoreceptors. Here, we sought to investigate whether additional mechanisms might contribute to the dynamic regulation of excitability of 5-HT neurons during the course of SSRI treatments. Borrowing from the well-described homeostatic strengthening of glutamatergic synapses onto cortical pyramidal neurons following prolonged periods of inactivity, we hypothesized that a similar homeostatic-like regulation of synaptic strength might be operant on 5-HT cells during an SSRI treatment. To test this possibility, we used whole-cell electrophysiological recordings on acute midbrain slices to monitor glutamatergic synapses onto 5-HT neurons. We found that a two-day treatment with the SSRI citalopram induced a robust reduction in both the amplitude and frequency of AMPAR-mediated mEPSCs. We also show that this depression in synaptic strength, induced by an SSRI, is transient since excitatory drive onto 5-HT neurons was enhanced by 7 days of treatments. Altogether, these results document a dynamic regulation of glutamatergic synaptic transmission during the time course of a prolonged treatment with an SSRI. Further elucidation of the cellular and molecular mechanisms driving this synaptic plasticity might identify novel pharmacological target to shorten the delay of antidepressant action.

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Pollnow, Stefan [Verfasser], and Olaf [Akademischer Betreuer] Dössel. "Characterizing Cardiac Electrophysiology during Radiofrequency Ablation : An Integrative Ex vivo, In silico, and In vivo Approach / Stefan Pollnow ; Betreuer: Olaf Dössel." Karlsruhe : KIT Scientific Publishing, 2019. http://d-nb.info/1186145404/34.

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Klimas, Aleksandra. "High-Throughput All-Optical Cardiac Electrophysiology| Design, Validation, and Applications in vitro and in vivo." Thesis, The George Washington University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10621781.

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Biological systems are inherently dynamic, requiring active interrogation and recording to provide a full understanding of their underlying mechanics. In order to fully characterize such a system, both readily quantifiable signals as well as a means of dynamic control are necessary. In the heart, the propagation of electrical waves driving contraction are mediated by the flow of ions through various ion channels working in concert to drive de- and re-polarization of the cell membrane. Typically, the culprit of electrical dysfunction in the heart is due to some disruption of normal function of one or more of these ion channels. In order to study these complex electrical disturbances, known as arrhythmias, high spatiotemporal resolution imaging and interrogation are necessary.

Traditional methods of interrogation have relied on the use of electrodes and patch clamp methods, which are inherently low throughput and have limited spatial resolution. Additionally, these approaches do not lend well for in vivo use. While studies of cardiac tissue have also employed optical mapping techniques where voltage- or calcium-sensitive fluorescent reporters provide detailed information about cell activation, repolarization, and wave propagation maps, stimulation has remained primarily limited to electrical means. However, recently developed optogenetic tools provide a means of high-spatiotemporal resolution (and potentially tissue-type specific) means of interrogation. By combining both of these methods, high-spatiotemporal dynamic characterization of cardiac electrophysiology can be achieved.

Here we present how all-optical approaches can be achieved via employing optogenetics in order to explore cardiac electrophysiology at the in vitro as well as in vivo scale. The main optical design is first implemented for in vitro use, where we demonstrate how OptoDyCE, our all-optical dynamic cardiac electrophysiology platform, can be used to screen drug effects in both isolated primary myocytes and human induced pluripotent stem-cell derived cardiomyocytes (hiPSC-CMs) grown in monolayers and 3D tissue constructs. We then characterize an upgraded version of OptoDyCE, capable of simultaneous imaging of membrane voltage and intracellular calcium signals. The system is used for screening of 12 blinded compounds to demonstrate how the platform can used for pro-arrhythmia prediction at the high-throughput (HT) scale. All compounds were properly identified as ‘safe’ or ‘unsafe’ using the multi-parameter endpoints, made possible with high-spatiotemporal resolution recordings under spontaneous and paced conditions. To further demonstrate how all-optical approaches improve proarrhythmia prediction, we tested vanoxerine, a compound that failed Phase III clinical trials, and demonstrate OptoDyCE’s ability to easily identify the compound as pro-arrhythmic, unlike techniques employing patch clamp and in silico modeling that deemed the compound safe for use in humans. As hiPSC-CMs provide a novel testbed for drug testing and disease modeling, we then use OptoDyCE to characterize these cells, both in terms of their potential immaturity (a common criticism) and their ability to recapitulate genetic diseases for use in disease modeling. Finally, the requirements for translating OptoDyCE for in vivo use are considered, and successful demonstration in vivo expression of ChR2 in the rat heart by employing systemic viral delivery, providing a model for development and testing of an optical system in intact tissue and for long-term use in behaving animals. Ultimately, we demonstrate the OptoDyCE platform has capacity to revolutionize pre-clinical drug testing, reduce cost, reduce animal use, and make clinically implemented personalized medicine an obtainable goal.

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Ponente, Federico. "Enhanced recording paradigms and advanced analyses of peripheral nerve fibers SPiike software." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/672365.

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The aim of this work is to investigate the human nociceptive system at the peripheral level. Researchers are still debating how the pain perception arises from this very intricate network. The human perception is the most elusive part of our knowledge since different subsystems are involved. The external information such as noxious stimuli must be processed at the peripheral level and through signal cascades and transduction this signal must reach the brain. At the brain level the information is processed and some decisions are taken, such as the well-known fight-or-flight response. In the introduction, the author describes how the human nociceptive system works and in which way the noxious stimulus is converted into a signal understandable by the brain. Several cortical and subcortical areas are involved in this signal processing and going deeper in this assembly line the information becomes more abstracted. The whole pathway is fundamental for pain perception, however some diseases start at the peripheral level. This in turn makes wrong signals reaching the brain. The brain is then processing information that are not real and the responses do not suit with the needs. Therefore, the peripheral system must be investigated and understood firstly, since some central diseases may have a peripheral component as well. With this purpose in mind the microneurography technique has been used. This technique has got some complexity and a computer-aided system must be implemented. The hardware aims to filter out the noisy signal and perform recording and stimulation of the neural fibers. The software is instead used to make the stimulation and recording as automatic as possible in a way that researchers do not have to deal with a lot of parameters and steps to carry out this powerful but also time consuming technique. Some software are already available in the market however even if they work fine with slow conduction fibers such as C-fibers they cannot cope with faster neurons (e.g. Aδ fibers). The aim of this work is to create a software (i.e. SPiike) able to stimulate and record every type of fibers implementing advanced analysis technique as well. Furthermore, considering that some in vivo experiments have been pursued within the project to check the functionality of the software, more specifically in rats and mice, the comparison between human nociceptors and mouse nociceptors is depicted in this section. In the method section, the experimental approach is described step by step. This is composed by several systems that work together for the stimulation, recording and analysis of the neural fibers. The control and acquisition module is composed by the software and a data acquisition board that trigger the stimulator and record the filtered signal. The stimulation module is composed by a stimulator that can be tuned as wish through dedicated knobs. Then the stimulus is delivered to the animal model (or the human patient) and the signal is recorded though a microelectrode inserted into the sciatic nerve. The amplification module is filtering out the noisy signal and is feeding a audio monitor for helping the researcher during the insertion of the electrode inside the nerve and it provides support during the whole experiment giving insights on fiber discharges. In this section the whole setup is described in details as well as the devices needed for the recording. Furthermore, the software development that is the core of this project is described as well, with all the considerations that must be considered during coding. Indeed, the flow chart must be followed methodically in order to minimize bugs and errors that may arise in the final product. Thus a description of the compiler and the Matlab IDE is given along with system and software requirements for the making of the SPiike software. Eventually the explanation of embedded functionalities and capabilities of SPiike is depicted in the final part of this section. This software is indeed able to stimulate slow conducting fibers as well as faster ones, and enhanced analysis techniques such as supervised machine learning are implemented. In the results section, the graphical user interface of the Spiike software is reveled. It resembles the one of another software already available in the market, with a filtered signal and a raster plot embedded on it. However, this software is more user-friendly and it accounts with icons and drop-down menus that enhance the experience of the users during the use of the tool, making their interactions smooth and intuitive. The SPiike software is subdivide into two different tools, a recording module and a analysis module. The former allows the stimulation and recording of neural fibers with a stimulation frequency up to 1000Hz and some online analysis can be conducted to have insights on fibers type and behavior. The analysis module is instead a more powerful analysis environment that can retrieve the dataset recorded with the other module or with the LabChart software. Advanced analysis techniques are implemented in this module, this is meant to speed up fiber classification and analysis. Conclusion and discussion provide a overview on some results. These will be compared to those obtainable through other software available in the market. In this section, pros and cons of the new implemented software, SPiike, will be described as well.

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Kumbhare, Deepak. "ELECTROPHYSIOLOGY OF BASAL GANGLIA (BG) CIRCUITRY AND DYSTONIA AS A MODEL OF MOTOR CONTROL DYSFUNCTION." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4305.

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The basal ganglia (BG) is a complex set of heavily interconnected nuclei located in the central part of the brain that receives inputs from the several areas of the cortex and projects via the thalamus back to the prefrontal and motor cortical areas. Despite playing a significant part in multiple brain functions, the physiology of the BG and associated disorders like dystonia remain poorly understood. Dystonia is a devastating condition characterized by ineffective, twisting movements, prolonged co-contractions and contorted postures. Evidences suggest that it occurs due to abnormal discharge patterning in BG-thalamocortocal (BGTC) circuitry. The central purpose of this study was to understand the electrophysiology of BGTC circuitry and its role in motor control and dystonia. Toward this goal, an advanced multi-target multi-unit recording and analysis system was utilized, which allows simultaneous collection and analysis of multiple neuronal units from multiple brain nuclei. Over the cause of this work, neuronal data from the globus pallidus (GP), subthalamic nucleus (STN), entopenduncular nucleus (EP), pallidal receiving thalamus (VL) and motor cortex (MC) was collected from normal, lesioned and dystonic rats under awake, head restrained conditions. The results have shown that the neuronal population in BG nuclei (GP, STN and EP) were characterized by a dichotomy of firing patterns in normal rats which remains preserved in dystonic rats. Unlike normals, neurons in dystonic rat exhibit reduced mean firing rate, increased irregularity and burstiness at resting state. The chaotic changes that occurs in BG leads to inadequate hyperpolarization levels within the VL thalamic neurons resulting in a shift from the normal bursting mode to an abnormal tonic firing pattern. During movement, the dystonic EP generates abnormally synchronized and elongated burst duration which further corrupts the VL motor signals. It was finally concluded that the loss of specificity and temporal misalignment between motor neurons leads to corrupted signaling to the muscles resulting in dystonic behavior. Furthermore, this study reveals the importance of EP output in controlling firing modes occurring in the VL thalamus.

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Shim, Stacey. "Alterations of the Monoaminergic Systems in the Rat Brain by Sustained Administration of Carisbamate and Lamotrigine." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23478.

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Carisbamate (CRS) and lamotrigine (LTG) are anticonvulsants which act mainly on neuronal voltage-gated sodium channels, that have been shown to have antidepressant-like effects in animal models of depression. In vivo electrophysiological recordings were carried out following 2 and 14 days of CRS or LTG administration. Overall firing activity in the dorsal raphe, locus coeruleus and ventral tegmental area were decreased with CRS. Similarly, a decrease in the dorsal raphe was also observed with LTG. Despite these presynaptic decreases in firing activity, both anticonvulsants exhibited significant enhancement of serotonergic transmission in the hippocampus as demonstrated by increased tonic activation of postsynaptic 5-HT1A receptors. This may be attributed to the observed desensitization of the terminal 5-HT1B autoreceptors. This study suggests that the enhanced serotonergic effect may be associated with an antiglutamatergic effect, and may contribute to the antidepressant-like effect of CRS in the forced swim test and the antidepressant properties of LTG.

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21

Keefer, Edward W. "Unique applications of cultured neuronal networks in pharmacology, toxicology, and basic neuroscience." Thesis, University of North Texas, 2001. https://digital.library.unt.edu/ark:/67531/metadc2797/.

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This dissertation research explored the capabilities of neuronal networks grown on substrate integrated microelectrode arrays in vitro with emphasis on utilizing such preparations in three specific application domains: pharmacology and drug development, biosensors and neurotoxicology, and the study of burst and synaptic mechanisms. Chapter 1 details the testing of seven novel AChE inhibitors, demonstrating that neuronal networks rapidly detect small molecular differences in closely related compounds, and reveal information about their probable physiological effects that are not attainable through biochemical characterization alone. Chapter 2 shows how neuronal networks may be used to classify and characterize an unknown compound. The compound, trimethylol propane phosphate (TMPP) elicited changes in network activity that resembled those induced by bicuculline, a known epileptogenic. Further work determined that TMPP produces its effects on network activity through a competitive inhibition of the GABAA receptor. This demonstrates that neuronal networks can provide rapid, reliable warning of the presence of toxic substances, and from the manner in which the spontaneous activity changes provide information on the class of compound present and its potential physiological effects. Additional simple pharmacological tests can provide valuable information on primary mechanisms involved in the altered neuronal network responses. Chapter 3 explores the effects produced by a radical simplification of synaptic driving forces. With all synaptic interactions pharmacologically limited to those mediated through the NMDA synapse, spinal cord networks exhibited an extremely regular burst oscillation characterized by a period of 2.9 ± 0.3 s, with mean coefficients of variation of 3.7, 4.7, and 4.9 % for burst rate, burst duration, and inter-burst interval, respectively (16 separate cultures). The reliability of expression of this oscillation suggests that it may represent a fundamental mechanism of importance during periods of NMDA receptor dominated activity, such as embryonic and early postnatal development. NMDA synapse mediated activity produces a precise oscillatory state that allows the study of excitatory-coupled network dynamics, burst mechanisms, emergent network properties, and structure-function relationships.

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Cao, Tuoxin. "Hydrogen Peroxide and Pharmacological Agent Modulation of TRPV2 Channel Gating." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4848.

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Transient receptor potential vanilloid 2 channel (TRPV2) is a Ca2+-permeable ion channel that is highly expressed in leukocytes but is also present in skeletal and cardiac muscle and endocrine cells. The TRPV2 function is implicated in a number of physiological processes, including bacterial phagocytosis, pro-inflammatory cytokine production, cardiac hypertrophy, and cancer development. TRPV2 knockout mice exhibit a high incidence of perinatal mortality, arguing that the channel plays essential roles in physiology. Despite the importance of TRPV2 for normal homeostasis, the mechanisms that control TRPV2 gating in response to pharmacological agonists, heating, membrane stretch, bioactive lipids and reactive oxygen species (ROS) remain poorly understood. Here we demonstrate that TRPV2 is functionally expressed in microglia (i.e., ‘brain macrophages’) and the microglia-like BV-2 cell line, and demonstrate that the gating of an endogenous TRPV2-like conductance is positively modulated by the bacterial toxin lipopolysaccharide (LPS), which is known to cause pro-inflammatory (M1) activation and increase ROS production by NADPH oxidase. To determine how TRPV2 gating is modulated by ROS, we recorded single channel activity in inside-out patches excised from HEK-293 cells expressing GFP-rTRPV2. Unitary currents elicited by the TRPV2 agonist 2-aminophenyl borinate (2-APB) or cannabidiol (CBD) are linear in monovalent recording solutions and give rise to an estimated unitary conductance of ~100pS, which is similar to TRPV1 but significantly smaller than TRPV3. Intriguingly, we find that although TRPV2 is insensitive to ROS (in the form of exogenously applied H2O2) alone, apparent open probability is synergistically enhanced when H2O2 is applied together with CBD. We identify two intracellular Cys residues that are necessary for TRPV2 responses to H2O2 sensitivity and find that these residues are located close to one another, albeit in different subunits, in the TRPV2 structure, suggesting that ROS promote the formation of an inter-subunit disulfide bond that alters sensitivity to pharmacological agonists. We hypothesize that ROS-dependent modulation of TRPV2 activity may be an important contributor to pro-inflammatory activation of microglia underline central nervous system diseases and that TRPV2 antagonism could be a useful therapeutic strategy in the treatment of neuroinflammation.

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Kursu, O. E. (Olli-Erkki). "Micromotion compensation and a neural recording and stimulation system for electrophysiological measurements." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526210186.

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Abstract The goal of this thesis was to investigate and build new circuit solutions for electrophysiological measurements that would be used in biophysical research of nervous system and brain activity. The first aim was to build a micromotion compensation system that could compensate for the relative movement of measurement microelectrodes and neurons that can cause signal attenuation or even loss. The purpose of this work was to stabilize the microelectrode with respect to the preparation in order to achieve more stable measurements with small test animals, such as insects, rodents or reptiles. The movement is measured with a touch probe sensor and a feedback loop containing a piezoelectric actuator that adjusts the position of the electrode. A prototype micromotion compensation system was built and its performance was measured in a realistic measurement condition. The compensation system was used to reduce the motion of the probe to below 1 µm, resulting in up to 98% compensation below 10 Hz. The design of the micromotion compensation system took advantage of a preceding study on a piezoelectric bimorph actuator/sensor structure. This study is also presented in the thesis. Another aim of the research was to design and build an integrated multichannel neural signal recording system with stimulation capabilities. The circuit was designed to amplify, digitize and stream out data from extracellular neuronal signal measurements. The main target of the measurement system are action potential signals, which are a type of “digital communication” between nerve cells that evolution has produced. The waveform of these action potential signals is the focus of interest. To accomplish this measurement, the developed circuit contains preamplification, multiplexing, post-amplification, A/D conversion and control logic for the A/D converter and data transmission. The circuit is also externally programmable, and it contains DACs for tuning high-pass filter corner frequency, amplifier bias current and stimulation current. The implemented electronics have low noise, low power and small circuit area. The gain of the circuit is adjustable from 100 to 5000 and the high-pass filter corner frequency from 0.5 Hz to 900 Hz. The sample rate is 20.833 kSps and the data rate is 3.5 Mbps. The measured noise level of the circuit is 7.5μV (rms) (300 Hz - 10 kHz) and the whole chip consumes less than 2 mW of power. A 16-channel prototype chip with 0.35μm CMOS technology was manufactured and its performance was measured. Backend electronics containing a microcontroller supporting high-speed USB data transfer was also programmed for the system. The device was tested in real measurements of neuronal signals in a cockroach (Periplaneta americana) preparation, and reliable streaming of the recorded data to the PC verified its proper function
Tiivistelmä Tämän väitöskirjatyön tavoitteena oli kehittää mittaus- ja säätöjärjestelmiä aivotutkimuksen ja biofysiikan sovelluksiin. Ensimmäisenä tutkimuskokonaisuutena oli mittaus- ja säätöjärjestelmän kehittäminen, minkä tavoitteena oli mahdollistaa aivojen sähköisen signaloinnin mittaaminen mahdollisimman luonnollisessa tilassa olevilla koe-eläimillä (esim. hyönteiset, matelijat tai pienet nisäkkäät). Tätä varten kehitettiin aktiivinen liikekompensointimekanismi, jossa kosketusanturilla mitattiin aivokudoksen mikrometriluokan mekaanista liikettä ja kompensoitiin sähköistä mittausta suorittavan anturin ja aivon välinen suhteellinen liike liikuttamalla takaisinkytkentälenkissä olevaa pietsosähköistä aktuaattoria. Kompensointimekanismin toiminta testattiin realistisissa mittausolosuhteissa. Liikekompensoinnilla saatiin vähennettyä mittausanturin liikettä suhteessa kudokseen alle mikrometriin, maksimikompensoinnin ollessa noin 98 % alle 10 Hz:n taajuudella. Väitöskirjaan liitettiin pietsosähköisiin komponentteihin liittyen taustatiedoksi artikkeli aiemmin suunnitellusta pietsosähköisestä bimorph aktuaattori/sensori -komponentista. Toisen tutkimuskokonaisuuden muodosti suurten hermosolupopulaatioiden toiminnan mittaamiseen sekä stimulointiin kehitetty monikanavainen järjestelmä. Tärkeimpänä mittauskohteena työssä ovat ekstrasellulaariset aktiopotentiaalisignaalit, jotka ovat eräänlainen evoluution tuottama “digitaalinen” hermosolujen välinen kommunikaatiomenetelmä. Kiinnostuksen kohteena ovat näiden aktiopotentiaalisignaalien aaltomuodot. Mittauksia varten työssä kehitettiin hermosolujen solun ulkopuoliseen nesteeseen asetettaviin elektrodeihin kytkettävä elektroniikka, jolla pystytään sekä stimuloimaan että mittaamaan jokaista elektrodia. Suunniteltu vahvistinelektroniikka on matalakohinainen, matalatehoinen ja pienikokoinen. Mittausjärjestelmään on suunniteltu myös multipleksointi, A/D-muunninelektroniikka sekä ohjauslogiikka, joka sisältää muunnostulosten puskuroinnin integroidun piirin rekisteripankkeihin, SPI-liitynnän high-speed USB protokollaa tukevalle mikrokontrollerille sekä konfiguraatiorekistereitä, joihin SPI-väylän kautta kirjoittamalla voidaan säätää piirin vahvistusta, operaatiovahvistimien biasvirtoja, kaistanleveyttä sekä stimulaatiovirtojen voimakkuuksia. Piirin vahvistus on säädettävissä 100:n ja 5000:n välillä ja ylipäästösuodatuksen kulmataajuus välillä 0,5 Hz - 900 Hz. Piirin näytteistystaajuus on 20,833 kSps ja tiedonsiirtonopeus 3,5 Mbps. Piirin kohinatasoksi mitattiin 7,5 µV (rms) (300 Hz - 10 kHz) ja koko piirin tehonkulutukseksi alle 2 mW. Integroidusta piiristä valmistettiin 16-kanavainen prototyyppi 0,35 µm:n CMOS-teknologialla. Kehitetyn laitteen toiminta varmistettiin mittaamalla hermosignaaleja torakkapreparaatista (Periplaneta americana). Mittausdata siirrettiin onnistuneesti ja luotettavasti PC:lle

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24

Squirrell, Daniel. "An in vivo electrophysiological and computational analysis of hippocampal synaptic changes in the Alzheimer's disease mouse." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/an-in-vivo-electrophysiological-and-computational-analysis-of-hippocampal-synaptic-changes-in-the-alzheimers-disease-mouse(de740023-7d91-418a-8c88-1141b3cd81f3).html.

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Alzheimer’s disease (AD) is a neurodegenerative disorder resulting in the decline of cognitive function, memory formation and retrieval, and abrupt changes in personality. Damage to brain networks occur during prodromal stages of AD, prior to the development of clinical symptoms of dementia. Further characterising this state and identifying reliable biomarkers for early detection are priorities in AD research. I characterised neuronal changes within the dorsal CA1 and subiculum regions of the hippocampal formation (HF) in the well-characterised 3xTgAD mouse model of AD. These regions are well-established sites for early neurodegeneration in both AD patients and AD animal models. We inserted multi-electrode recording arrays into CA1 and subiculum of urethane anaesthetised 3xTgAD mice and recorded spontaneous local field potential activity. Using traditional and novel information theoretic approaches, I determined the information carrying capacity of the CA1- subiculum network during different network rhythms, and how this altered with age and AD-like pathology. A bipolar stimulating electrode was inserted into CA1, allowing the assessment of synaptic integrity between CA1 and subiculum. Results showed that synaptic and network changes occur in CA1 and subiculum during the early stages of AD-like pathology and correlates with the development of intracellular beta-amyloid. There is a progressive breakdown in synaptic facilitation as early as 3 months in the 3xTgAD mouse. These data support an advanced ageing-like phenotype in AD model mice, with an enhanced age/pathology-dependent breakdown in neuronal communication compared to age-matched controls. In agreement with other studies, 3xTgAD mice demonstrate evidence of pathology-related changes in the network rhythms of the HF. 3xTgAD mice show an increase in the power of alpha and beta rhythms, and a concurrent reduction in the power of delta oscillations. Application of novel information theoretic techniques results in a breakdown in the information carrying capacity of the hippocampal system. This deficit manifests as a reduction in information flow during delta-dominant periods of EEG rhythms, with a specific reduction during slow-wave ripple activity. This change in neuronal communication correlates with the onset of memory-retention/consolidation deficits. These network changes are complex, with alterations in the information carrying capacity of the system during theta rhythms at 6 months, and during slow-wave components by 9 months in the 3xTgAD mouse. This study provides the first evidence of an early and progressive decline in neuronal connectivity and communication that correlates with changes in cognition in the 3xTgAD mouse. Application of novel analytical techniques to multi-site EEG recording revealed early and measureable changes in information processing during the onset of AD-like pathology. These are important new biomarkers for early AD characterisation.

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Velmurugan, Sathya. "Actions of appetite regulating peptides on supraoptic nucleus (SON) oxytocin neurones." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3938.

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Oxytocin has established roles in parturition and lactation, but can also be released in response to non-reproductive stimuli, such as hyperosmolarity and stress. As a majority of appetite regulating peptides activate the hypothalamo-pituitary-adrenal stress axis, and oxytocin is also a stress hormone in the rat, it was hypothesized that the oxytocin system in the neurohypophysial axis could be a target for appetite-regulating peptides of central and peripheral origin. The effects of central administration of neuropeptide Y (NPY; a central orexigenic peptide and a central and peripheral neurotransmitter co-released with noradrenaline; n=5 rats) and systemic administration of secretin (a peripheral gut peptide belonging to the family of brain-gut peptides; n=26) and leptin (a peripheral anorexigenic peptide from adipose tissue; n=23) on the electrical activity of SON oxytocin neurones in vivo were studied in urethane-anaesthetized female rats with extracellular recording. Effects were compared with the excitatory responses to cholecystokinin (CCK; a peripheral anorexigenic gut peptide; n=45). Influences of fasting and pregnancy and effects of these peptides on the activity of SON vasopressin neurones were also studied. Results: (1) All the central and peripheral appetite peptides tested increased the electrical activity of SON oxytocin neurones. (a) NPY: Basal firing rate of 3.5 ± 1.05 (mean ± s.e.m) spikes/s was increased by 1 ± 0.45 spikes/s 1min after NPY (basal vs 0-10min post-NPY: P=0.03, paired t-test; n=5). (b) Secretin: Basal rate of 4.1 ± 0.4 spikes/s was increased by 1.7 ± 0.2 spikes/s 2.5min after secretin (basal vs 0-10min post-secretin: P<0.001, paired t-test; n=26). (c) Leptin: Basal rate of 3.4 ± 0.4 spikes/s was increased by 0.4 ± 0.08 spikes/s 1.5min after leptin (basal vs 0-10min post-leptin: P=0.01, paired t-test; n=23). (d) CCK: Basal rate of 3.6 ± 0.3 spikes/s was increased by 1.1 ± 0.15 spikes/s 1min after CCK (basal vs 0-10min post- CCK: P<0.001, Wilcoxon signed rank test; n=45). (2) Secretin induced excitatory responses were greater than to other peptides (P<0.001, Kruskal-Wallis one-way ANOVA on ranks). (3) Secretin dose-dependently increased SON oxytocin neurone electrical activity and peripheral oxytocin release in anaesthetized rats. (4) Intracerebroventricular infusion and microdialysis studies with benoxathian (α1 adrenergic antagonist) revealed that secretininduced excitation of SON oxytocin and vasopressin neurones involves central excitatory noradrenergic pathways. (5) Fasting for 18h did not alter the excitation of SON oxytocin neurones induced by secretin, CCK and leptin. (6) The pathway leading to excitation of oxytocin neurones by CCK was not influenced by prior leptin administration. (7) SON oxytocin neurones were responsive to leptin during late pregnancy. (8) NPY-induced excitation of oxytocin neurones was intact in anaesthetised late pregnant rats, contrasting with attenuated oxytocin secretory responses observed previously in conscious rats. (9) Systemic NPY excited SON oxytocin neurones. (10) Systemic CCK administration either inhibited (77%) or did not affect (23%) SON vasopressin neurones, while leptin had no significant effect, and responses to secretin were predominantly excitatory (67%). Systemic NPY inhibited vasopressin neurones, but central NPY was ineffective. Conclusion: Appetite peptides target SON oxytocin neurones. Postprandially released secretin and leptin might, like CCK, induce peripheral oxytocin release, so as to regulate water and electrolyte homeostasis, which is inevitably disturbed during feeding. Any central release of oxytocin induced by these peptides, might regulate feeding behaviour and satiety. Oxytocin neurone excitation induced by NPY may be relevant during stress responses.

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Schweigmann, Michael [Verfasser]. "Versatile LCP surface microelectrodes for combining electrophysiology and in vivo two-photon imaging in the murine CNS / Michael Schweigmann." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1232240095/34.

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27

Jiang, Jojo L. "Alterations of the Monoaminergic Systems by Sustained Triple Reuptake Inhibition." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23171.

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Recent approaches in depression therapeutics include triple reuptake inhibitors, drugs that target three monoamine systems. Using in vivo electrophysiological and microdialysis techniques, the effects of 2- and 14-day treatments of escitalopram, nomifensine and the co-administration of these two drugs (TRI) were examined in male Sprague-Dawley rats. Short- and long-term TRI administration decreased NE firing and had no effect on DA neurons. Normal 5-HT firing rates were maintained after 2-day TRI administration compared to the robust inhibitory action of selective serotonin reuptake inhibitors (SSRIs). Escitalopram treatment enhanced the tonic activation of the 5-HT1A receptors given the increase in firing observed following WAY100635 administration. Nomifensine treatment enhanced tonic activation of the α2–adrenoceptors following idazoxan administration. TRI treatment caused a robust increase in extracellular DA levels that was in part mediated by a serotonergic contribution. Therapeutic effects of the drugs examined in this study may be due to the enhancement of 5-HT, NE and/or DA neurotransmission.

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Iro, Chidiebere Michael. "Investigation of the Mechanisms of Action of Ketamine on the Monoamine Systems: Electrophysiological Studies on the Rat Brain." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39910.

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Background: A single infusion of ketamine has rapid antidepressant properties, although the drawback is a lack of sustained effect. A previous study showed a rapid enhancement (within 2 hours) in ventral tegmental area (VTA) dopamine (DA) neuron population and locus coeruleus (LC) norepinephrine (NE) firing and bursting activity following a single ketamine administration. The current study investigated whether these changes are present 24 hours after a single administration and if they are maintained with repeated administration. Additionally, we examined dorsal raphe nucleus (DRN) serotonin (5-HT) neurons to assess the effects of single and repeated ketamine administration on these neurons. Methods: Ketamine (10 mg/kg, i.p.) was administered to male Sprague Dawley rats once or repeatedly (3 times/week) for 2 weeks. After single and repeated administration of ketamine, electrophysiological recordings were done in the VTA, LC and DRN in anesthetized rats, 24 hrs, 3 or 7 days post-administration. Spike frequency, bursting, and for VTA neurons, spontaneously active neurons/trajectory were assessed. Results: In the VTA, LC and DRN, 24 hrs after ketamine was injected acutely there was no significant difference between controls and treated animals in all parameters assessed. However, after repeated administration, there was an increase in bursting and number of spontaneously discharging neurons per tract of VTA DA neurons as well as an increase in frequency of discharge of LC NE neurons. While the increased number of spontaneously discharging neurons per tract had dissipated after 3 days, the enhanced bursting was still present but dissipated after 7 days. As for LC NE neurons, the increased frequency of discharge was no longer present after 3 days. No significant differences in the firing of DRN 5-HT neurons were observed between controls and treated animals even after ketamine was administered repeatedly. Conclusion: These results indicate that repeated but not acute administration of ketamine maintained the increase in population activity of DA neurons and firing activity of NE neurons.

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Tiwari, Ekta. "ASSESSMENT OF CANINE BLADDER FUNCTION RESTORATION USING BEHAVIORAL MONITORING AND IN-VIVO ELECTROPHYSIOLOGICAL TECHNIQUES." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/590674.

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Electrical and Computer Engineering
Ph.D.
Spinal cord injuries and other neurological disorders can disturb the regulation of normal bladder function including continence and micturition. Developing new neuronal pathways by surgically rerouting nerves is a potential approach for restoring bladder function. Our laboratory successfully rerouted somatic nerves to the anterior vesical branch of the pelvic nerve to reinnervate the bladder muscle in canines. Electrical stimulation of these transferred nerves induced detrusor pressure and bladder emptying and we confirmed regrowth of these rerouted nerves using retrograde neurotracing methods. In these studies, reinnervation was proved at 1st and 3rd months after decentralization. We believe that our aim of developing an approach to surgically reinnervate the bladder after long-term decentralization is critical to the success of the reinnervation surgery due to the possibility that patients would delay having a surgery until they try other non-surgical approaches or therapies. We also demonstrated the reinnervation of urethral and anal sphincters by femoral to pudendal nerve transfer after sacral ventral root transection to restore continence. However, these studies did not demonstrate the reinnervation of bladder, urethra and anal sphincter, all in same animal that would be helpful to human patients with lower motor neuron lesioned bladders to restore both continence and emptying. Therefore, prior to applying these surgical procedures to human patients, further investigation is required to prove the effectiveness of nerve transfer strategies in this canine model using multiple experimental techniques. This dissertation is a part of a larger project in canines examining whether surgical rerouting of obturator to pelvic nerve and sciatic to pudendal nerve allows restoration of bladder, urethral and anal sphincter functions, including continence (storage) and emptying (voiding and defecation) functions, in lower motor neuron lesioned bladders. In this study, it was aimed to explore bladder and urethral reinnervation using behavioral observation and in-vivo electrophysiological techniques. In order to completely prove that the reinnervation surgeries are responsible for restoration of bladder and urethral functions, it was first necessary to demonstrate the absence of these functions in animals with long term decentralized bladders and to determine whether the same animals were able to recover functions after reinnervation. In specific aim 1, we addressed this goal by tracking squat-and-void behaviors at monthly intervals after decentralization and reinnervation, using home cage video recordings and evaluation of bladder sensation and emptying after bladder filling. Immediately prior to euthanasia, reinnervation was also explored by electrical stimulation of transferred nerves to evaluate motor function. Retrograde neuronal tracing was also performed to explore sensory reinnervation. Results showed evidence of functional restoration of bladder and urethral function in reinnervated animals based on behavior observation and electrical stimulation of transferred nerves. Also, regrowth of neuronal cells in the new neuronal pathways was observed that were developed by the nerve transfer surgeries. This study also aimed to establish an electroneurogram recording method (part of in-vivo electrophysiological experiments) to explore afferent (sensory) neuronal activity in transferred nerves induced by bladder filling. However, the extraction of neuronal activity from the peripheral nerves is a challenging task. Several factors including noise, interference from surrounding muscle activities and the electronic components can affect these microvolts level recordings. Choice of recording electrode in configuration with the whole recording setup also plays a significant role while performing these low amplitude signal recordings. In specific aim 2, we addressed this issue by refining electroneurogram recording techniques to obtain high strength signal during multifiber recording. We first developed custom electrodes, suitable for varying nerve diameters and available implantation sites, were tested for functionality. Then, we performed multiple testing using these electrodes with different amplifiers to calibrate noise in saline. Testing results helped to establish the recording setup suitable for in-vivo experimental environment. Later, these refined techniques were applied to record afferent (sensory) activity of sciatic nerves and afferent (sensory) and efferent (motor) activity of hypogastric nerves in rats. Based on the recording results, it was aimed to employ similar techniques in order to record nerve activity in the canine model. Prior to applying these refined techniques to explore sensory reinnervation from new neuronal pathways after nerve transfer surgeries, in specific aim 3, we aimed to assess the hypogastric nerve activity in normal intact and acutely lumbosacral decentralized bladders using these refined techniques. The effects of electrical stimulation of hypogastric nerves or lumbar roots on detrusor pressure were determined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was recorded using custom-made bipolar cuff electrodes during bladder filling. To confirm or refute that any increase in electroneurogram during bladder filling is due to afferent activity from the end organ, the hypogastric nerve was transected between the recording electrode and the spinal cord and the effects of bladder filling on afferent but not efferent activity were recorded. Results showed that electrical stimulation of hypogastric nerves evoked low amplitude detrusor pressures that did not differ between the two anesthetics. Upper lumbar (L2) ventral root stimulation evoked detrusor pressures were suppressed, yet not eliminated after transection of hypogastric nerves and all spinal roots below L5. Afferent and efferent hypogastric nerve activity did not change with bladder filling in neuronally intact bladders but decreased in decentralized bladders. No change in afferent activity were observed during bladder filling in normal intact and decentralized bladders. Overall findings in this research indicate that the new neuronal pathways created by nerve transfer can restore bladder sensation and emptying function in lower motor neuron-lesioned canines. A more complete decentralized bladder model needs to include transection of both the lumbosacral spinal roots innervating the bladder and the hypogastric nerves prior to performing nerve transfer surgeries. The refined electroneurogram recording methods may be suitable for evaluating the effectiveness of nerve transfer surgeries by monitoring the sensory activities of the transferred nerve.
Temple University--Theses

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30

Pospischil, Martin. "Interaction between synaptic conductances and action potential initiation in cortical neurons : computational models and analysis of intracellular recording." Paris 6, 2007. http://www.theses.fr/2007PA066647.

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Pendants les etats naturels d'activite in vivo, les neurones neocorticaux sont sujets a une conductance membranaire forte et fluctuante. Cependant, les proprietes integratives des neurones ne sont pas connues pendant ces etats de "haute conductance" (HC). Nous avons (1) caracterise le lien entre la dynamique des conductances et l'initiation du potentiel d'action (PA) dans les neurones corticaux dans les etats HC; (2) compare differents modeles de reponse de PA (PSTH) pendant ces etats. Nous distinguons deux modes de decharge, selon que le PA est evoque par une augmentation d'excitation ou par une diminution d'inhibition. Nous avons propose une nouvelle methode pour calculer les "spike-triggered average" (STA) des conductances a partir du potentiel membranaire, teste cette methode numeriquement et in vitro, ainsi que applique cette methode aux enregistrements in vivo. Nous demontrons que les PAs inhibiteurs sont majoritaires chez le chat eveille, ce qui revele un role majeur de l'inhibition

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Halpern, Jeffrey Mark. "Non-Planar Diamond Electrodes for Biomedical Neural Sensing and Stimulating." Cleveland, Ohio : Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1269612139.

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Thesis (Doctor of Philosophy)--Case Western Reserve University, 2010
Department of Chemical Engineering Title from PDF (viewed on 2010-05-25) Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center

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Davis, Katherine. "Hippocampal dysfunction in the 3xTgAD mouse model of Alzheimer's disease." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/hippocampal-dysfunction-in-the-3xtgad-mouse-model-of-alzheimers-disease(ba2d4704-9e22-4213-8bc7-a1c55a0e0ccd).html.

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Alzheimer’s disease (AD) is a neurodegenerative disorder, characterised by severe memory loss and the accumulation of amyloid-beta (Aβ) and tau pathology within neocortex and medial temporal lobe (MTL) structures. Episodic memory impairment is a defining feature of early AD. The hippocampal formation (HF), a major network involved in both memory formation and retrieval is one of the first areas affected by AD pathology. However, the aetiology of AD is unknown; specifically how Aβ and tau pathologies cause memory impairment and how the physiological function of HF is affected. In this thesis, the 3xTgAD mouse was used as a high fidelity model of human AD pathological progression to study the function of HF during early (intracellular Aβ) and more progressive (extracellular plaque and hyperphosphorylated tau pathology) AD stages, referred to as ‘young’ and ‘old’ respectively. Specifically we: i) applied the hippocampal-dependent What-Where-Which (WWWhich) task to study the onset and progression of episodic-like memory decline (previously uncharacterised in the 3xTgAD mouse); ii) examined allocentric spatial memory in radial arm water maze (RAWM) and spontaneous alternation (SA) behaviour in T-Maze to discern whether cognitive differences exist between spontaneous and negatively reinforced tasks (the latter could be influenced by an exaggerated stress response); and iii) performed electrophysiological recordings in vivo from the HF of urethane-anaesthetised 3xTgAD and control mice to study basic synaptic connectivity, short-term synaptic plasticity and neuronal reverberation across the CA1-DG axis using a multi-site electrode. Our results showed an early and specific deficit for WWWhich episodic-like memory in the 3xTgAD model, with a decline in performance witnessed in mice as young as 3 months. In contrast, 3xTgAD component memory comprising single or dual associations of ‘What’, ‘Where’, ‘Which’ and ‘When’ remained intact suggesting the episodic impairment was due to dysfunction during the association of three component information streams within hippocampus (Chapters 3 and 4). 3xTgAD mice were equally impaired for allocentric spatial memory in RAWM and in their SA behaviour, suggesting no inherent advantage of examining cognition in paradigms which elicit behavioural distress (Chapter 5). We witnessed the development of subtle synaptic abnormalities in young 3xTgAD mice in the form of enhanced short-term paired pulse facilitation in CA1 and DG, however, a paucity of response facilitation in CA1 in response to train stimulation. In contrast, we saw intact basic synaptic function (fibre integrity and synaptic connectivity) in 3xTgAD mice of both young and old ages, suggesting gross hippocampal circuitry remained in place (Chapter 6). Finally, we saw an effect of normal ageing on cognition in the WWWhich and spatial tasks (Chapters 4 and 5), and a decline in neuronal reverberation with age in control and 3xTgAD mice. Dysfunction in these two parameters (behavioural and electrophysiological) coincided with the onset of intracellular Aβ accumulation within HF in 3xTgAD mice. This suggests a role of intracellular Aβ in impairing the physiological function of HF in AD which translates as cognitive decline in hippocampal-dependent forms of memory. Episodic memory was found to be especially sensitive to AD-related pathology and impairment, thus the WWWhich task may be applied to faithfully study the onset of cognitive decline in other AD mouse models. Further examination of the relative contribution of Aβ to hippocampal dysfunction in the 3xTgAD model is required.

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Malezieux, Meryl. "Dynamique intracellulaire des cellules pyramidales de CA3 dans l'hippocampe pendant les états de veille." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0317/document.

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Les états de veille sont composés d’états cérébraux distincts, corrélés avec différents comportements et caractérisés par des oscillations spécifiques observables dans le potentiel de champ local (Local Field Potential, LFP). Bien que les différents états cérébraux et leur signature dans le LFP aient été caractérisés, les mécanismes cellulaires sous-jacents restent à ce jour peu connus. Des changements des propriétés de neurones uniques seraient corrélés avec, et pourraient participer à la génération de ces changements d’états cérébraux. L’activité coordonnée et synchronisée de neurones facilite certains processus cognitifs tels que la mémoire. L’hippocampe joue un rôle essentiel dans les mémoires spatiale et épisodique, et dans l’hippocampe, CA3 est important pour la formation d’associations facilitant l’encodage rapide de la mémoire. De plus, les informations provenant du cortex entorhinal, du gyrus denté, et de CA3 même sont comparées et intégrées dans CA3 avant d’être transmises à CA1. Lors de périodes de repos, le LFP hippocampique présente une activité large et irrégulière (Large Irregular Activity, LIA), ponctuée par des oscillations plus rapides, les sharp-wave ripples, jouant un rôle dans la consolidation de la mémoire. Lors de périodes exploratoires, le LFP hippocampique oscille aux fréquences theta (6-12 Hz) et gamma (30-100 Hz). Les cellules pyramidales (CP) de CA3 jouent un rôle important dans chacun de ces états ; elles sont nécessaires pour les sharp wave lors de périodes de repos, et les oscillations gamma lors de comportements exploratoires. Dans le but d’étudier les modulations intracellulaires des CP de CA3, nous avons réalisé des enregistrements de patch-clamp en configuration cellule entière chez l’animal éveillé. Nous avons associé ces enregistrements avec des mesures du diamètre pupillaire et de la vitesse de locomotion de l’animal, ainsi qu’avec l’enregistrement de l’activité oscillatoire du LFP dans l’hippocampe. Nos résultats montrent que certaines CP de CA3 sont sensibles à la modulation intracellulaire lors de différents rythmes hippocampiques, et ont tendance à diminuer leur potentiel de membrane moyen, leur excitabilité, leur variance et leur décharge de potentiel d’action lors des oscillations theta par rapport aux périodes de LIA. De futures études permettront de déterminer si ces changements sont dus à des changements d’entrées synaptiques et/ou de neuromodulateurs. Ces modulations pourraient jouer un rôle dans l’émergence des rythmes oscillatoires du LFP, et permettre à CA3 de réaliser différentes fonctions mnésiques à différents moments
Wakefulness is comprised of distinct brain states, correlated with different behaviors and characterized by specific oscillatory patterns in the local field potential (LFP). While much work has characterized different brain states and their LFP signatures, the underlying cellular mechanisms are less known. Changes in single cell properties are thought to correlate with and possibly result in these changes in brain state. Synchronized and coordinated activity among distributed neurons supports cognitive processes such as memory. The hippocampus is essential for spatial and episodic memory, and within the hippocampus, area CA3 is important for rapid encoding of one-trial memory. Additionally, CA3 is the site where information from the entorhinal cortex, dentate gyrus, and CA3 itself is compared and integrated before output to CA1. During quiet wakefulness, the hippocampal LFP displays large irregular activity (LIA) punctuated by sharp-wave ripples, which play a role in memory consolidation. During exploratory behaviors, hippocampal LFP oscillates at both theta and gamma frequencies. CA3 pyramidal cells (PCs) play an important role in each of these brain states; they are necessary for both sharp waves during quiet wakefulness and for gamma oscillations during exploratory behavior. We explored the changes that occur in the intracellular dynamics of CA3 PCs during changes in brain state, by using whole-cell patch-clamp recordings from CA3 PCs in awake head-fixed mice. We combined those recordings with measurements of pupil diameter, treadmill running speed and LFP recordings of oscillatory activity. Our findings show that some CA3 PCs are prone to intracellular modulation during brain rhythms, and tend to decrease their average membrane potential, excitability, variance and output firing during theta as compared to LIA. Future studies will demonstrate whether these effects are due to changes in synaptic and/or neuromodulatory inputs. This modulation at the single-cell level in CA3 could play a role in the emergence of oscillations, and underlie the ability of CA3 to perform different memory functions during different brain states

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Hanini-Daoud, Maroua. "Traitement des informations thalamiques au travers des ganglions de la base : approche électrophysiologique et optogénétique in vivo." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4109.

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Le centre médian/parafasciculaire (CM/Pf) du thalamus a récemment émergé comme un élément d'intérêt dans le contexte de la maladie de Parkinson. Ainsi le fonctionnement normal et pathologique des GB ne peut pas être pleinement élucidé sans qu'il ne soit pris en considération. Dans ce contexte, nous avons analysé le transfert des informations thalamiques dans les GB en enregistrant, in vivo, les réponses évoquées au niveau de la structure de sortie des GB, la substantce noire pars reticulata (SNr) soit par la stimulation électrique ou optogénétique du CM/Pf. Ensuite, nous avons étudié les composantes des GB impliquées dans ces réponses en analysant les réponses évoquées par l'activation optogenetique spécifique des voies thalamo-striée, thalamo-subthalamique ou thalamo-nigrale. À la fois l'activation électrique et optogenetique du CM/Pf évoquent des réponses complexes dans la SNr qui sont composées d'une inhibition qui peut être précédée et/ou suivie d'excitations. L'inhibition et l'excitation tardive dépendent de l'activation des voies trans-striatales, alors que les premières excitations mettent en jeu les voies thalamo-subthalamique et thalamo-nigrale. Nous avons également étudié l'impact des interneurones cholinergiques du striatum ainsi que les afférences dopaminergiques sur le transfert des informations thalamiques dans les GB. Pour ce faire, nous avons enregistré les réponses évoquées au niveau des neurones de projection du striatum suite à la stimulation électrique du CM/Pf avec ou sans l'inhibition optogénétique des CINs. Nous serons alors en mesure de déterminer comment les CINs sont impliqués dans le transfert des informations thalamiques au sein des GB
The centre median/parafascicular (CM/Pf) of the thalamus has recently emerged as a component of interest in the context of Parkinson’s disease. Thus normal and pathological dynamics of BG cannot be fully understood unless it is taken into account. Here, we analyzed the transfer of CM/Pf information through BG by recording, in vivo, the evoked responses of BG output neurons in the substantia nigra pars reticulata (SNr) to either electrical or optogenetic CM/Pf stimulations. Then, we investigated the BG components involved in these responses by analyzing the responses evoked by specific optogenetic activation of the thalamo-striatal, thalamo-subthalamic or thalamo-nigral pathways. Both electrical and optogenetic activation of CM/Pf evoke complex responses in SNr that are composed of an inhibition that can be preceded and/or followed by excitations. The inhibition and the late excitation rely on the activation of the trans-striatal pathways, whereas the early excitations involve thalamo-subthalamic and thalamo-nigral projections. We are currently analyzing whether and how the striatal cholinergic interneurons (CINs) and the dopaminergic afferent system modulate the transfer of thalamic information within the BG. For the second part of my project, we analyzed the treatment of thalamic information from CM/Pf at the level of the striatum. To do this, we recorded the evoked responses of striatal projection neurons by the electrical stimulation of the CM/Pf with or without the inhibition of the CINs by optogenetics. We will then be able to determine how CINs are involved in the transfer of thalamic information at the level of the striatum

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Danysz, Wojciech, Gunnar Flik, Andrew McCreary, Carsten Tober, Wilfried Dimpfel, Jean C. Bizot, Richard Kostrzewa, et al. "Effects of Sarizotan in Animal Models of ADHD: Challenging Pharmacokinetic–Pharmacodynamic Relationships." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/948.

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Sarizotan 1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-[[5-(4-fluorophenyl) pyridin-3-yl]methyl] methenamine, showed an in vivo pharmaco-EEG profile resembling that of methylphenidate which is used in attention deficit/hyperactivity disorder (ADHD). In turn, we tested sarizotan against impulsivity in juvenile rats measuring the choice for large delayed vs. a small immediate reward in a T-maze and obtained encouraging results starting at 0.03 mg/kg (plasma levels of ~11 nM). Results from rats treated neonatally with 6-hydroxydopamine (6-OHDA), also supported anti-ADHD activity although starting at 0.3 mg/kg. However, microdialysis studies revealed that free brain concentration of sarizotan at active doses were below its affinity for 5-HT1A receptors, the assumed primary target. In contrast, electrophysiological experiments in mid-brain Raphé serotonergic cells paralleled by plasma sampling showed that there was ~60 % inhibition of firing rate—indicating significant activation of 5-HT1A receptors—at a plasma concentration of 76 nM. In line with this, we observed that sarizotan concentrations in brain homogenates were similar to total blood levels but over 500 fold higher than free extracellular fluid (ECF) concentrations as measured using brain microdialysis. These data suggest that sarizotan may have potential anti-ADHD effects at low doses free of the previously reported side-effects. Moreover, in this case a classical pharmacokinetic–pharmacodynamic relationship based on free brain concentrations seems to be less appropriate than target engagement pharmacodynamic readouts.

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Ridler, Thomas. "Entorhinal cortex dysfunction in rodent models of dementia." Thesis, University of Exeter, 2017. http://hdl.handle.net/10871/30575.

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As both the major input and output of the hippocampal formation, the entorhinal cortex (EC) occupies a pivotal position in the medial temporal lobe. The discovery of grid cells in the medial entorhinal cortex (mEC) has led to this region being widely implicated in spatial information processing. Importantly, the EC is also the first area affected by dementia pathology, with neurons appearing particularly susceptible to degeneration. Despite this, little is known about how pathology affects the functional output of mEC neurons, either in their ability to coordinate firing to produce network oscillations, or to represent information regarding the external environment. This thesis will use electrophysiological techniques to examine how dementia pathology contributes to the breakdown of mEC neuronal networks using the rTg4510 mouse model of tauopathy. The first 2 results chapters will show how the anatomical organisation along the dorso-ventral axis of the mEC has profound influence on the network activity that can be observed both in brain slices and awake-behaving mice. It will further show how deficits in network activity in rTg4510 mice occur differentially across this axis, with dorsal mEC appearing more vulnerable to changes in oscillatory function than ventral. The third results chapter will begin to explore the relationship between global network activity and the external environment, showing that rTg4510 mice display clear deficits in the relationship between oscillation properties and locomotor activity. Finally, the underlying basis for these changes will be examined, through the recording of single-unit activity in these mice. It will show a decreased tendency for mEC neurons to display firing rates modulated by running speed, as well as an almost complete breakdown of grid cell periodicity after periods of tau overexpression. Understanding how dementia pathology produces changes to neuronal function and ultimately cognition is key for understanding and treating the disease. This thesis will therefore provide novel insights into the dysfunction of the EC during dementia pathology.

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Van, Rheede Joram Jacob. "The emergence of visual responses in the developing retinotectal system in vivo." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:57cb9bff-a085-4ac4-b413-c29112eeb78e.

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Patterned neuronal activity driven by the sensory environment plays a key role in the development of precise synaptic connectivity in the brain. It is well established that the action potentials (‘spikes’) generated by individual neurons are crucial to this developmental process. A neuron’s spiking activity is jointly determined by its synaptic inputs and its intrinsic excitability. It is therefore important to ask how a neuron develops these attributes, and whether the emergence of spiking might itself be governed by activity-dependent processes. In this thesis, I address these questions in the retinotectal system of Xenopus laevis. First, I investigate the extent to which visuospatial information is available to the developing retinotectal system. I show that the eyes of developing Xenopus larvae are hyperopic at the onset of vision, but rapidly grow towards correct vision. Despite its imperfect optics, the Xenopus eye is able to generate spatially restricted activity on the retina, which is evident in the spatial structure of the receptive fields (RFs) of tectal neurons. Using a novel method to map the visually driven spiking output and synaptic inputs of the same tectal neuron in vivo, I show that neuronal spiking activity closely follows the spatiotemporal profile of glutamatergic inputs. Next, I characterise a population of neurons in the developing optic tectum that does not fire action potentials, despite receiving visually evoked glutamatergic and γ-aminobutyric acid (GABA)ergic synaptic inputs. A comparison of visually spiking and visually non-spiking neurons reveals that the principal reason these neurons are ‘silent’ is that they lack sufficient glutamatergic synaptic excitation. In the final section of the thesis, I investigate whether visually driven activity can play a role in the ‘unsilencing’ of these silent neurons. I show that non-spiking tectal neurons can be rapidly converted into spiking neurons through a visual conditioning protocol. This conversion is associated with a selective increase in glutamatergic input and implicates a novel, spike-independent form of synaptic potentiation. I provide evidence that this novel plasticity process is mediated by GABAergic inputs that are depolarising during early development, and can act in synergy with N-methyl-D-aspartate receptors (NMDARs) to strengthen immature glutamatergic synapses. Consistent with this, preventing the depolarising effects of GABA or blocking NMDARs abolished the activity-dependent unsilencing of tectal neurons. These results therefore support a model in which GABAergic and glutamatergic transmitter systems function synergistically to enable a neuron to recruit the synaptic excitation it needs to develop sensory-driven spiking activity. This represents a transition with important consequences for both the functional output and the activity-dependent development of a neuron.

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Dubanet, Olivier. "Dynamique des interactions entre excitation et inhibition périsomatique dans le circuit hippocampique normal et épileptique in vivo." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0259.

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L'hippocampe est une structure essentielle pour les processus d’apprentissage et la mémoire. Le fonctionnement de ce circuit neuronal repose sur des interactions complexes entre cellules pyramidales glutamatergiques excitatrices et divers types d'interneurones GABAergiques inhibiteurs, dont on connait mal les rôles exacts car il est très difficile d'étudier in vivo la fonction inhibitrice issue d'interneurones spécifiques. L'altération des interactions synaptiques entre cellules pyramidales et interneurones de l'hippocampe est de plus à la base de pathologies neurologiques telle que l'épilepsie, neurodéveloppementales telle que l'autisme, ou neurodégénératives telle que la maladie d'Alzheimer. Parmi les différents types d'interneurones, ceux qui expriment la parvalbumine (PV) et dont l'axone projette sur les corps cellulaires (inhibition périsomatique) des cellules pyramidales ont une organisation anatomique qui les rend particulièrement efficaces pour bloquer la décharge de potentiels d'action chez leurs cellules cibles. C'est la raison pour laquelle on considère qu'ils jouent un rôle particulièrement important non seulement dans le codage de l'information (en contrôlant quelle cellule est en mesure ou non de décharger) mais aussi dans l'équilibre du circuit, pour éviter que l'excitation réciproque entre cellules pyramidales ne dégénère en crise d'épilepsie. L'efficacité de cette inhibition dite périsomatique dépend largement du gradient électrochimique des ions chlorure (Cl-), c'est à dire la combinaison entre le potentiel membranaire et la répartition des ions Cl- entre l'intérieur et l'extérieur du neurone cible. Or, ces paramètres ne cessent de changer au fil de l'activité neuronale, et il a même été démontré que le gradient Cl- pouvait s'inverser, générant un effet paradoxalement excitateur de la transmission GABAergique. Ce phénomène, qui participerait à la mise en place physiologique des circuits neuronaux immatures, est aujourd'hui également considéré comme une source majeure de dérèglement des circuits neuronaux dans diverses pathologies comme l'épilepsie, l'autisme ou la schizophrénie. Il s'agit donc d'un champs de recherche aux implications cliniques directes, et la recherche de drogues permettant de restaurer un gradient Cl- physiologique représente un espoir thérapeutique majeur, mais les données contradictoires de la littérature appellent à la recherche d'une évaluation directe, qui n'a pas été réalisée jusque-là faute de disposer d'une approche technique adéquate. Pendant ma thèse, par des techniques d'électrophysiologie, d’opto- et de pharmaco-génétique, j'ai contribué à la mise au point d'une nouvelle approche méthodologique sophistiquée d'évaluation de la transmission GABAergique périsomatique dans l'hippocampe, à même de respecter la complexité des dynamiques de l'activité neuronale spontanée in vivo. Mon travail de thèse a consisté à étudier le rôle fonctionnel des interneurones parvalbumine (PV) de l'inhibition périsomatique dans le circuit hipocampique adulte, dans les conditions physiologiques et dans deux modèles d'épilepsie chez la souris. J'ai ainsi pu détecter in vivo l'expression d'un GABA excitateur mais qui ne semble pas participer à la génération des crises aigues car exprimé dans la période de silence post-ictale, ni à l'épileptogénèse car exprimé seulement de façon anecdotique une semaine post-status epilepticus, un stade auquel j'ai également observé que la majorité des neurones pyramidaux de CA3 n'étaient plus sous contrôle inhibiteur périsomatique. En plus de contribuer à mieux comprendre l'épileptogénèse, ces travaux pourraient servir de modèle pour l'évaluation de la contribution d'un GABA excitateur à diverses conditions pathologiques, et de l'efficacité réelle de diverses approches visant à moduler le gradient chlore pour restaurer une fonction inhibitrice in vivo
The hippocampus is a key structure for learning and memory. The function of this neuronal circuit is based on complex interactions between excitatory glutamatergic pyramidal cells and various types of inhibitory GABAergic interneurons. The precise roles fullfiled by interneuron subtypes is still unclear because it is challenging to study in vivo the inhibitory function of specific interneurons. Alterations of the synaptic interactions between pyramidal cells and interneurons in the hippocampus also underlie neurological pathologies such as epilepsy, neurodevelopmental diseases such as autism, or neurodegenerative diseases such as Alzheimer's disease. Among the different types of interneurons, those that express parvalbumin (PV) and project to pyramidal cell bodies (perisomatic inhibition) are particularly efficient in blocking action potential generation in their target cells. PV interneurons therefore play a central role in neuronal coding (by controlling which cell can fire or not) but also in the balance between global excitation and inhibition within the circuit, prevention runaway excitation between interconnected pyramidal cells and the generation of epileptic seizure. Functional perisomatic inhibition directly depends on Cl- electrochemical gradient, or the interaction between membrane potential and Cl- distribution across the membrane of the target neuron. However, these parameters change continuously during neuronal activity, and it has been shown that the Cl- gradient can be reversed, resulting in paradoxically excitatory GABAergic transmission. This phenomenon, which contributes to the physiological maturation of neuronal circuits during early development, is also considered as a major source of neuronal circuit dysfunction in various pathologies such as epilepsy, autism or schizophrenia. This field of research is therefore clinically relevant, and the research for drugs restoring a physiological Cl- gradient is very active. However, a direct assessment of the excitatory GABA hypothesis has been hindered by the technical difficulty of probing endogenous GABAergic synaptic function in vivo, and contradictory data in the literature call for a direct evaluation. During my PhD, using electrophysiological, opto- and pharmaco-genetic techniques, I have contributed to develop a new and sophisticated methodological approach to evaluate the perisomatic GABAergic transmission in the hippocampus, respecting the complexity of spontaneous neuronal activity dynamics in vivo. I have studied the functional role of perisomatic inhibition from PV interneurons in the adult hippocampal circuit, in physiological conditions and in two models of epileptic mice in which I was able to detect an excitatory GABAergic transmission in vivo. However, excitatory GABA was unlikely to participate in epileptogenesis because it was expressed only during the period of post-ictal silence after acute seizures, or in a potentially negligible minority of pyramidal cells one week post-status epilepticus during the latent period that precedes the emergence of chronic epilepsy, a stage during which I also demonstrated that the majority of CA3 pyramidal neurons were no longer under perisomatic inhibitory control. In addition to contribute to a better understanding of epileptogenesis, this approach constitutes an invaluable tool to quantify the actual in vivo efficacy of drugs designed to modulate Cl- homeostasis and restore physiological GABAergic inhibition, thereby meeting high clinical and therapeutical expectations

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39

Castagnola, Valentina. "Implantable microelectrodes on soft substrate with nanostructured active surface for stimulation and recording of brain activities." Toulouse 3, 2014. http://thesesups.ups-tlse.fr/2646/.

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Les prothèses neuronales implantables offrent de nos jours une réelle opportunité pour restaurer des fonctions perdues par des patients atteints de lésions cérébrales ou de la moelle épinière, en associant un canal non-musculaire au cerveau ce qui permet la connexion de machines au système nerveux. La fiabilité sur le long terme de ces dispositifs, se présentant sous la forme d'électrodes implantables, est un facteur crucial pour envisager des applications dans le domaine des interfaces cerveau-machine. Cependant, les électrodes actuelles pour l'enregistrement et la stimulation se détériorent en quelques mois voire quelques semaines. Ce défaut de fiabilité sur le long terme, principalement lié à une réaction chronique contre un corps étranger, est induit au départ par le traumatisme consécutif à l'insertion du dispositif et s'aggrave ensuite, durant les mouvements du cerveau, à cause des propriétés mécaniques inadaptées de l'électrode par rapport à celles du tissu. Au cours du temps, l'ensemble de ces facteurs inflammatoires conduit à l'encapsulation de l'électrode par une couche isolante de cellules réactives détériorant ainsi la qualité de l'interface entre le dispositif implanté et le tissu cérébral. Pour s'affranchir de ce phénomène, la biocompatibilité des matériaux et des procédés, ainsi que les propriétés mécaniques de l'électrode doivent être pris en considération. Durant cette thèse, nous avons abordé la question en développant un procédé de fabrication simple pour réaliser des dispositifs implantables souples en parylène. Les électrodes flexibles ainsi obtenues sont totalement biocompatibles et leur compliance est adaptée à celle du tissu cérébral ce qui limite fortement la réaction inflammatoire occasionnée par les mouvements du cerveau. Après avoir optimisé le procédé de fabrication, nous avons focalisé notre étude sur les performances du dispositif et sa stabilité. L'utilisation d'une grande densité d'électrodes micrométriques, avec un diamètre de 10 à 50 µm, permet de localiser les zones d'enregistrement en rendant possible, par exemple, la conversion d'un ensemble de signaux électrophysiologiques en une commande de mouvement. En contrepartie, la réduction de la taille des électrodes conduit à une augmentation de l'impédance ce qui dégrade la qualité d'enregistrement des signaux. Ici, un polymère conducteur organique, le poly(3,4-ethylenedioxythiophene), PEDOT, a été utilisé pour améliorer les caractéristiques électriques d'enregistrement d'électrodes de petites dimensions. Le PEDOT a été déposé sur la surface des électrodes par électrochimie avec une grande reproductibilité. Des dépôts homogènes avec des conductivités électriques très élevées ont été obtenus en utilisant différents procédés électrochimiques. Grâce à l'augmentation du rapport surface/volume induit par la présence de la couche de PEDOT, une diminution significative de l'impédance de l'électrode (jusqu'à 3 ordres de grandeur) a été obtenue sur une large plage de fréquences. De tests de vieillissement thermique accéléré ont également été effectués sans influence notable sur les propriétés électriques démontrant ainsi la stabilité de la couche de PEDOT durant plusieurs mois. Les dispositifs ainsi obtenus, fabriqués en parylène avec un dépôt de PEDOT sur la surface active des électrodes, ont été testés in vitro et in vivo sur des cerveaux de souris. Un meilleur rapport signal sur bruit a été mesuré durant des enregistrements neuronaux en comparaison avec des résultats obtenus avec des électrodes commerciales. En conclusion, la technologie décrite ici, associant stabilité sur le long terme et faible impédance, a permis d'obtenir des électrodes implantables parfaitement adaptées pour le développement d'interfaces neuronales chroniques
Implantable neural prosthetics devices offer, nowadays, a promising opportunity for the restoration of lost functions in patients affected by brain or spinal cord injury, by providing the brain with a non-muscular channel able to link machines to the nervous system. The long term reliability of these devices constituted by implantable electrodes has emerged as a crucial factor in view of the application in the "brain-machine interface" domain. However, current electrodes for recording or stimulation still fail within months or even weeks. This lack of long-term reliability, mainly related to the chronic foreign body reaction, is induced, at the beginning, by insertion trauma, and then exacerbated as a result of mechanical mismatch between the electrode and the tissue during brain motion. All these inflammatory factors lead, over the time, to the encapsulation of the electrode by an insulating layer of reactive cells thus impacting the quality of the interface between the implanted device and the brain tissue. To overcome this phenomenon, both the biocompatibility of materials and processes, and the mechanical properties of the electrodes have to be considered. During this PhD, we have addressed both issues by developing a simple process to fabricate soft implantable devices fully made of parylene. The resulting flexible electrodes are fully biocompatible and more compliant with the brain tissue thus limiting the inflammatory reaction during brain motions. Once the fabrication process has been completed, our study has been focused on the device performances and stability. The use of high density micrometer electrodes with a diameter ranging from 10 to 50 µm, on one hand, provides more localized recordings and allows converting a series of electrophysiological signals into, for instance, a movement command. On the other hand, as the electrode dimensions decrease, the impedance increases affecting the quality of signal recordings. Here, an organic conductive polymer, the poly(3,4-ethylenedioxythiophene), PEDOT, has been used to improve the recording characteristics of small electrodes. PEDOT was deposited on electrode surfaces by electrochemical deposition with a high reproducibility. Homogeneous coatings with a high electrical conductivity were obtained using various electrochemical routes. Thanks to the increase of the surface to volume ratio provided by the PEDOT coating, a significant lowering of the electrode impedance (up to 3 orders of magnitude) has been obtained over a wide range of frequencies. Thermal accelerated ageing tests were also performed without any significant impact on the electrical properties demonstrating the stability of the PEDOT coatings over several months. The resulting devices, made of parylene with a PEDOT coating on the active surface of electrodes, have been tested in vitro and in vivo in mice brain. An improved signal to noise ratio during neural recording has been measured in comparison to results obtained with commercially available electrodes. In conclusion, the technology described here, combining long-term stability and low impedance, make these implantable electrodes suitable candidates for the development of chronic neural interfaces

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40

Gao, Xiaojie. "Regulation and functions of burst firing: the role of KCNQ3 potassium channels in vivo." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/22144.

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Ionenkanäle leiten Ionenströme über neuronale Membranen, wodurch Aktionspotentiale erzeugt und weitergeleitet werden. Sie spielen eine zentrale Rolle bei der Regulierung der Erregbarkeit und des Aktivierungsverhaltens von Neuronen. KCNQs sind eine wichtige Familie von spannungsgesteuerten Kaliumkanälen; ihre Dysfunktion kann zu verschiedenen neurologischen Krankheiten führen, einschließlich Erkrankung an Epilepsie und Taubheit. Es wurde gezeigt, dass KCNQ2 und KCNQ3 den M-Strom verantwortlich sind. Letzterer ist für die Regulierung des repetitiven Feuerns von Pyramidenzellen entscheidend. Im Gegensatz zu KCNQ2, ist die funktionelle Bedeutung von KCNQ3 noch nicht aufgeklärt. In dieser Arbeit zeigen wir mittels extrazellulärer Elektrophysiologie in vivo, dass bei konstitutiven Kcnq3 Knockoutmäusen die hippokampalen Pyramidenzellen vermehrt burstartig feuern. Außerdem weisen diese Tiere eine verminderte Spike-Frequenz-Anpassung auf und die Wahrscheinlichkeit des Burst-Feuerns während zwei verschiedener Oszillationen – Theta gegen Nicht-Theta – kann nicht mehr unterscheiden werden. Des Weiteren zeigen Kcnq3-Knockout- Pyramidenzellen während der Theta-Oszillation weder eine dominante Phasenpräferenz, noch eine Koordination ihrer Burst-Feuerung. Die Thetawellen Phasenpräzision tritt weiterhin bei dem vorübergehend verstärkten Feuern auf. Das räumliche selektive Feuern von mutmaßlichen Ortszellen blieb auch bei den Knockout-Mäusen erhalten, aber es ist hauptsächlich vom Burst- Feuern abhängig. Diese Studie zeigt, dass der KCNQ3-Ionenkanal eine wichtige Rolle bei der Regulierung der neuronalen Erregbarkeit und der Informationsverarbeitung spielt, und gibt damit Einblicke in die Bedeutsamkeit der KCNQ3-Ionenkanäle bezüglich der neurologischen Störungen.
Ion channels conduct ion flows across neuronal membrane whereby action potential is generated and propagated. They play a central role in regulating the excitability and firing behavior of a neuron. Among them, the KCNQs present a prominent family of voltage-gated potassium channels. Dysfunction of KCNQ2–5 channels can lead to varied neurological diseases including early onset epilepsy and deafness. In cortex and hippocampus, KCNQ2 and KCNQ3 have been demonstrated to underlie the non-inactivating M-current critical for controlling the repetitive firing of pyramidal cells. However, the functional significance of KCNQ3, unlike that of KCNQ2, remains elusive. Here, by applying in vivo extracellular electrophysiology in Kcnq3 constitutive knockout mice and the wild-type littermates, we find that hippocampal pyramidal cells lacking KCNQ3 exhibit increased burst firing. Moreover, the spike frequency adaptation of their bursts is diminished, and the burst propensity during two different field oscillations – theta versus non-theta – becomes indistinguishable. During theta oscillations, Kcnq3 knockout pyramidal cells no longer display unimodal phase preference and do not coordinate their burst firing. But phase advancement along successive theta cycles continues to occur at times of transiently intensified firing. The selective firing of place cells is largely preserved in the knockout while mainly relying on bursts. These results suggest that KCNQ3 channels indeed play a significant and specific role in regulating the neurons’ excitability and information processing, thus providing crucial mechanistic insights into the relevance of the KCNQ3 channels in neurological disorders.

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Rodríguez, Salinas Roberto Javier. "El uso e impacto de las técnicas de grabación y mezcla analógica en la producción musical estadounidense de pop y rock (2011-2017): Alternativas para su aplicación en el estudio digital." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2020. http://hdl.handle.net/10757/654919.

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El presente trabajo de investigación trata de identificar y analizar la influencia y la aplicación del audio analógico en la producción musical contemporánea, abarcando diversos criterios: sonoro/técnico, de ejecución, social, de preservación o archivo, entre otros. A pesar de que el audio digital, y el uso derivado de las herramientas de edición y mezcla, se consideran el estándar en la industria musical actual, se conoce que un número importante de productores, ingenieros y artistas siguen empleando hoy en día las técnicas de grabación y mezcla analógica desarrolladas décadas atrás. Por ello, el audio analógico surge como una alternativa a los procesos de creación y producción musical modernos, tanto a nivel sonoro como de ejecución. Este trabajo parte del desarrollo técnico y estético en la grabación analógica, realizando comparaciones con su contraparte digital. Para ello, se toman en cuenta las opiniones y los procesos de producción de productores musicales y profesionales a cargo de las producciones discográficas más relevantes en los últimos años en el circuito norteamericano. Es en estas producciones donde se evidencia el uso creativo del audio analógico, así como su adaptación al entorno digital. Finalmente, se tiene en cuenta al productor independiente como principal beneficiario de esta publicación, quien conoce directa o indirectamente los beneficios del audio analógico, pero no necesariamente cuenta con los recursos para integrarlo a su estación de trabajo. Por ello, se busca brindar herramientas y soluciones para poder emplear e integrar las principales funciones del formato analógico y digital en una producción moderna.
The hereby thesis attempts to identify and analyze the influence and application of analog audio in contemporary music production by covering diverse criteria: sonic/technical, performative, social, of preservation or archive, among others. Although digital audio, and its derived use of editing and mixing tools, are currently considered standard in the music industry, it is also known that a significant number of producers, engineers and artists still employ analog recording and mixing techniques developed decades ago. Hence, analog audio presents itself as an alternative to the modern creative and production processes, at both sonic and performance levels. This work begins with the technical and aesthetical development within an analog recording, comparing it afterwards with its digital counterpart. To serve this purpose, the opinion and detailed production processes of renowned American producers and professionals, responsible for the most acclaimed records in the last ten years, are taken into consideration. Those records evidence the creative use of analog audio, as well as its adaptation to a digital setup. Finally, independent producers could benefit the most from the information and arguments in this paper, because they directly or indirectly know the benefits of working analog, even when they often lack the resources to acquire these tools. Therefore, the author attempts to bring tools and solutions for the application of analog and digital audio in a single modern production.
Tesis

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42

Bienvenu, Thomas Claude Michel. "Functional specialisation of GABAergic cells in the basolateral amygdala." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:d52fb5ad-19cc-41b8-a1e2-2f25ef82dddf.

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The amygdala, in particular its basolateral part (BLA), plays a critical role in binding affective qualities to otherwise neutral stimuli, and in eliciting emotional behaviors. Plasticity of inputs to BLA projection neurons involved in emotional memory has been extensively studied. However, how BLA neurons collectively process sensory information to encode and stabilize emotional memories is unknown. Precise coordination of BLA network activities seems critical. Specifically, timed integration of salient stimuli, and synchrony with hippocampal theta oscillations appear to be important. Recent reports suggest that GABAergic neurons may be instrumental in shaping ensemble activity in the BLA. Studies of neocortex and hippocampus showed that diverse GABAergic interneuron types play highly specific roles in coordinating network operations. The presence of similar interneuron populations in the BLA suggests comparable mechanism may govern its activities. However, GABAergic cell types and their functions have not been characterized.

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Vitrac, Clément. "Contrôle dopaminergique de la motricité au niveau cortical et striatal." Thesis, Poitiers, 2014. http://www.theses.fr/2014POIT2282/document.

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Le cortex moteur primaire et le striatum permettent la planification et la sélection de mouvements. La dopamine régule l'activité des neurones dans ces deux structures. La perte des neurones à dopamine projetant de la substance noire compacte vers le striatum est à l'origine de troubles moteurs observés dans la maladie de Parkinson. Nous avons caractérisé le contrôle par la dopamine des neurones du cortex moteur primaire chez la souris et avons démontré que les fibres dopaminergiques innervent préférentiellement la représentation des membres antérieurs dans les couches corticales profondes. Nous avons montré que la dopamine module localement l’activité électrophysiologique des neurones cortico-striataux via les récepteurs D2. Ces résultats montrent que la dopamine peut exercer un contrôle direct sur la motricité au niveau des neurones du cortex moteur primaire. Nous avons par la suite déterminé le potentiel des thérapies cellulaires dans un modèle animal de la maladie de Parkinson. Les approches actuelles privilégient la greffe ectopique de neurones à dopamine dans la région cible, le striatum. Nous avons choisi une approche alternative consistant à pratiquer la greffe au niveau de la région lésée, la substance noire compacte. Nous avons montré chez la souris que la lésion des neurones dopaminergiques altère les propriétés électrophysiologiques des neurones du striatum et que la greffe homotopique de neurones entraîne une meilleure récupération de ces caractéristiques électrophysiologiques que la greffe ectopique dans le striatum.Ces résultats ouvrent des perspectives d'étude des effets de la greffe homotopique sur l'activité des autres structures contrôlant la motricité
Primary motor cortex and striatum are involved in movement planification and selection. Dopamine regulates the neuronal activity of these two structures. The motor impairments observed in Parkinson's disease originates from the loss of dopamine neurons projecting from the substantia nigra pars compacta to the striatum.We characterized the dopaminergic control of the neurons of primary motor cortex in mice and we demonstrated that dopaminergic fibers preferentially innervate the forelimb representation map in the deep cortical layers. Furthermore, we demonstrated that dopamine locally modulates the electrophysiological activity of the cortico-striatal neurons through D2 receptors. These results show that dopamine can directly control motor function by influencing neuronal activity in primary motor cortex.Thereafter, we determined the potential of cell replacement therapies in an animal model of Parkinson's disease. In most studies, the transplanted dopamine neurons have been placed within the striatum. We have chosen an alternative approach by grafting neurons into the lesioned nucleus, substantia nigra. We showed in mice that the lesion of dopaminergic neurons impaired the electrophysiological properties of the striatal neurons. Whereas these properties are not fully restored with an intra-striatal transplant, all the electrophysiological characteristics are recovered with an intra-nigral graft. This result opens new perspectives to study the homotopic graft effects on the activity of the other structures controlling motor function

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Thomazeau, Aurore. "Dysfonctions synaptiques glutamatergiques dans le cortex préfrontal de modèles murins de trisomie 21 surexprimant le gène Dyrk1a et stratégies thérapeutiques." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR21921/document.

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La trisomie 21 est la première cause de retard mental, phénotype majeur de la maladie. Elle est due à la présence d’un chromosome 21 supplémentaire. De nombreux gènes sont présents sur ce chromosome mais quelques-uns ont été proposés comme candidats pour les phénotypes neurocognitifs associés à la maladie, notamment le gène Dyrk1a. Il code pour une sérine-thréonine kinase, DYRK1A, à rôle majeur dans le développement cérébral et l’activité synaptique. Le cortex préfrontal sous-tend un ensemble de fonctions cognitives supérieures dont les fonctions exécutives et est impliqué dans la régulation du comportement émotionnel et de l’humeur, composantes largement affectées dans la trisomie 21. Ce travail de thèse a permis de caractériser des défauts majeurs de la transmission et la plasticité synaptique glutamatergique au sein du cortex préfrontal de deux modèles murins différents de trisomie 21: le modèle mBACtgDyrk1a surexprimant le gène murin Dyrk1a et le modèle Ts65Dn surexprimant 130 gènes de l’analogue murin du chromosome 21 dont Dyrk1a. Un autre versant de l’étude a concerné l’utilisation d’un composé inhibiteur de l’activité DYRK1A ou d’autres cibles cellulaires pour corriger les altérations préfrontales observées, constituant ainsi de nouvelles pistes thérapeutiques pour les phénotypes neurocognitifs associés à la trisomie 21
Down syndrome is the major cause of mental retardation, the main phenotype of the pathology. It is due to an extra chromosome 21. Many genes have been proposed as candidates for the neurocognitive phenotypes of Down syndrome, notably Dyrk1a. It encodes the serine-threonine kinase DYRK1A which is involved in brain development and synaptic functions. The prefrontal cortex mediates higher cognitive functions, such as executive functions and emotional regulation. This study highlighted major deficits in prefrontal cortex glutamatergic transmission and plasticity of two mouse models for Down syndrome: the overexpressing Dyrk1a mBACtgDyrk1a model and the Ts65Dn model, overexpressing around 130 murine orthologous genes of HSAS21 chromosome. Another aspect of this study was the development of new effective therapeutic strategy for Down syndrome neurocognitive phenotypes based on DYRK1A or other cellular targets activity inhibition

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Cabanas, Magali. "Modification des activités de réseaux in vivo chez un modèle murin de la maladie de Huntington." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0345/document.

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La maladie de Huntington est une pathologie héréditaire qui se caractérise par une dégénérescence sélective des neurones striataux de la voie indirecte des ganglions de la base. Chez les patients ainsi que chez les souris modèles de la pathologie, en plus des symptômes moteurs, cognitifs et psychiatriques, des troubles du sommeil peuvent aussi apparaitre dès la phase pré-symptomatique. L’étude électrophysiologique in vivo des souris transgéniques R6/1a, en outre, révélé en début de phase symptomatique l’apparition du rythme pathologique β observé principalement durant le sommeil. Ces travaux de thèses ont donc eut pour but d’étudier le lien entre les modifications d’activités de réseaux cérébraux, les troubles du sommeil et l’émergence du rythme β ainsi que l’implication de ces anomalies dans les perturbations comportementales observées chez les souris R6/1. Notre étude de l’imagerie c-Fos a montré une hyperactivation de la voie frontostriatale chez ces souris, et ceci uniquement au stade pré-symptomatique sans aucune modification d’activation de la voie indirecte. Notre étude pharmacogénétique a démontré que la modification d’activité de ces neurones de projection striataux pouvait modifier l’alternance veille/sommeil mais ne pouvaient générer le rythme β. Enfin, notre étude pharmacologique a établit le lien entre le dysfonctionnement du système orexinergique et l’émergence du rythme β chez les souris R6/1. Ces travaux ont permis de mieux décrire des modifications d’activités de réseaux associées aux différents stades de la pathologie, en particulier au stade présymptomatique, et leurs contributions aux troubles du sommeil et l’émergence du rythme β
Huntington’s disease (HD) is an inherited pathology that causes selective degeneration ofindirect striatal pathway neurons of the basal ganglia. In addition to the classic motor,cognitive and psychiatric symptoms, patients and mouse models of HD develop sleepdisorders, which can appear at as early as pre-symptomatic stage. Furthermore, in vivoelectrophysiological study of R6/1 transgenic mice revealed a unique and pathological βrhythm that appear at early symptomatic stage and which is mainly observed during sleep.The aim of this thesis work was to examine the link between changes in cerebral networkactivities, sleep disturbances and β rhythm, and to determine the contribution of theseabnormalities to the behavioral disturbances observed in R6/1 mice. Our neuroimaging study of the marker of neuronal activity c-Fos showed a hyperactivation of frontostriatal pathway at pre-symptomatic stage without any activity changes of the vulnerable indirect pathway neurons. Our pharmacogenetic study demonstrated that changes of striatal projection neuronal activity can modify sleep/wake behaviors, without inducing the pathological β rhythm. Finally, our pharmacological study established a link between orexinergic system dysfunction and β rhythm emergence in R6/1 mice. Our data, therefore, described further the natures of altered neural circuit activity associated with different disease stages, in particular pre-motor symptomatic period, and the importance of these alterations for sleep disturbances as well as β rhythm appearance in transgenic HD mice

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Carus-Cadavieco, Marta. "Coordination of innate behaviors by GABAergic cells in lateral hypothalamus." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19135.

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Der laterale Hypothalamus (LH) reguliert angeborene Verhaltensweisen. Ob und wie die Koordination von hypothalamischen Neuronengruppen Verhaltensübergänge reguliert, blieb jedoch unbekannt. In dieser Arbeit wurde Optogenetik mit neuronalen Ableitungen in verhaltenden Mäusen kombiniert. LHVgat Neurone erhöhten ihre Aktivitätsrate während Übergängen vom NREM-Schlaf zum Wachzustand. LHVgat Zellen projizieren zum Nucleus reticularis des Thalamus (RTN). Optogenetische Aktivierung von Vgat Ausgängen im RTN führte eine starke, frequenzabhängige Inhibierung von RTN Zellen herbei und replizierte Verhaltenszustands-abhängige Aktivitätsraten in RTN Neuronen. Ableitungen von LH Neuronen während Umgebungserkundung ergaben, dass 65% der LH Neurone ihre Aktivitätsrate erhöhten, wenn das Tier began sich fortzubewegen. 'Top-down’ Vorderhirn Innervation des LH erfolgt größtenteils durch Signale ausgehend vom lateralen Septums (LS). Während spontaner Umgebungserkundung und freiem Zugang zu Futter wiesen der LH und das LS Gamma-Oszillationen (30-90 Hz) auf, welche neuronale Aktivität innerhalb und zwischen diesen beiden Gehirnregionen synchronisierten. Optogenetische Stimulation von Somatostatin-positiven GABAergen Projektionen zum LH mit Gamma-Frequenz förderte die Nahrungssuche und erhöhte die Wahrscheinlichkeit des Betretens der Nahrungszone. Inhibitorische Signale des LS bewirkten eine Unterteilung der LH Neurone: entsprechend ihrer Aktivität im Bezug zur Nahrungsstelle wurden sie während bestimmter Phasen der Gamma-Oszillation aktiviert. Dabei führte optogenetische Stimulation von LS-LH Neuronen mit Gamma-Frequenz keine Veränderung bei der Nahrungsaufnahme selbst herbei. Insgesamt liefert diese Arbeit neue Einsichten über die Funktion der neuronalen Netzwerke des LH, welche durch Signalgebung mit unterschiedlichen Zeitskalen über die Koordination mit vor- und nachgeschalteten neuronalen Netzwerken Übergange zwischen verschiedenen angeborenen Verhaltensweisen regeln.
Lateral hypothalamus (LH) is crucial for regulation of innate behaviors. However, it remained unknown whether and how temporal coordination of hypothalamic neuronal populations regulates behavioral transitions. This work combined optogenetics with neuronal recordings in behaving mice. LHVgat cells were optogenetically identified. LHVgat neurons increased firing rates upon transitions from non-REM (NREM) sleep to wakefulness, and their optogenetic stimulation during NREM sleep induced a fast transition to wakefulness. LHVgat cells project to the reticular thalamic nucleus (RTN). Optogenetic activation of LHVgat terminals in the RTN exerted a strong frequency-dependent inhibition of RTN cells and replicated state-dependent changes in RTN neurons activity. Recordings of LH neurons during exploration revealed that 65% of LH neurons increased their activity upon the onset of locomotion. Top-down forebrain innervation of LH is provided, to a great extent, by inhibitory inputs from the lateral septum (LS). During spontaneous exploration in a free-feeding model, LS and LH displayed prominent gamma oscillations (30-90 Hz) which entrained neuronal activity within and across the two regions. Optogenetic gamma-frequency stimulation of somatostatin-positive GABAergic projections to LH facilitated food-seeking, and increased the probability of entering the food zone. LS inhibitory input enabled separate signaling by LH neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. In contrast to increased food intake during optogenetic stimulation of LHVgat cells, food intake during gamma-rhythmic LS-LH stimulation was not changed. Overall this works provides new insight into the function of LH circuitry, that employs signalling at different time scales, which, in coordination with upstream and downstream circuits, regulates transitions between innate behaviors.

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47

Ziebro, Thomas R. "In vivo PPy(DBS) sensors to quantify excitability of cells via sodium fluctuations in extracellular solution." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492031927557033.

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48

Delestrée, Nicolas. "Excitabilité intrinsèque, couverture synaptique et vacuolisation dendritique des motoneurones spinaux chez la souris SOD1-G93A, modèle de la Sclérose Latérale Amyotrophique." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T035/document.

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Les motoneurones tiennent une place remarquable dans l'organisme : ils constituent l'interface entre le système nerveux central et le système musculaire. Leur excitabilité est une caractéristique primordiale dans le comportement moteur puisqu'elle définit la force musculaire développée en réponse à la commande motrice. Chez la souris, la décharge des motoneurones est marquée par la présence d'oscillations de mode mixte (MMOs) entre les potentiels d'action. Ces MMOs permettent la décharge des motoneurones à basse fréquence et sont responsables d'un régime de décharge particulier nommé zone sous-Primaire, pendant lequel la fréquence de décharge est très variable et le gain de la relation courant-Fréquence élevé. Nous avons étudié les mécanismes responsables de l'apparition de ces MMOs à la fois de manière expérimentale, dans une préparation in vivo de souris anesthésié, incluant l'utilisation du Dynamic Clamp, et théorique, au moyen d'un modèle mono-Compartimental de motoneurone. Nos résultats ont montré que ces MMOs étaient causées par les courants sodiques et potassiques responsables des potentiels d'action et qu'elles émergeaient d'un état de faible excitabilité de la membrane, dû à l'inactivation lente des courants sodiques. Nous avons également montré que le courant de post-Hyperpolarisation pouvait paradoxalement augmenter l’excitabilité des motoneurones et réduire les MMOs en dé-Inactivant le courant sodique. La Sclérose Latérale Amyotrophique (SLA) conduit à la dégénérescence spécifique de ces motoneurones qui s'accompagne d'une vacuolisation de leur arborisation dendritique. L'augmentation précoce de l'excitabilité des motoneurones dans la maladie a largement été évoquée pour rendre compte de leur atteinte. Une hyperexcitabilité, aussi bien d'origine intrinsèque qu'extrinsèque pourrait en effet produire une excitotoxicité délétère pour la cellule. Si une telle modification de l'excitabilité est en cause dans la maladie, elle devrait persister jusqu'aux âges auxquels se produisent les premières dénervations des jonctions neuromusculaires. Nous avons enregistré les propriétés électrophysiologiques des motoneurones dans une préparation in vivo de souris adultes SOD1-G93A, modèle de la SLA. Nos résultats ont montré que leur conductance d'entrée était augmentée dans les jours qui précèdent les premières dénervations de leurs jonctions neuromusculaires. Malgré cela, leur excitabilité n'était pas modifiée. Loin d'être intrinsèquement hyperexcitables, une fraction d'entre eux perdaient même leur capacité à décharger de manière répétée. Nous avons finalement étudié la vacuolisation qui prend place dans les dendrites des motoneurones au cours de la maladie et son lien avec la couverture synaptique. Nous avons montré que la vacuolisation dendritique prenait place avant les dénervations et que la taille des vacuoles augmentait avec l'âge des souris SOD1-G93A. De manière intéressante, cette progression semblait plus rapide dans les motoneurones les plus sensibles à la maladie. Bien que la couverture synaptique n'était pas modifiée au cours de la maladie, nous avons mis en évidence une densité de synapses excitatrices et inhibitrices plus importante sur les régions dendritiques qui se vacuolisent. Ces résultats suggèrent un lien entre l'activité synaptique et la formation de vacuoles dans les motoneurones au cours de la SLA. Les motoneurones ne présentant pas d'hyperexcitabilité intrinsèque, une excitotoxicité d'origine synaptique pourrait alors être responsable de leur dégénérescence
Motoneurones hold a remarkable position in the organism: they are the interface between the central nervous system and the muscular system. Their excitability is a crucial characteristic in motor behavior since it determines the muscular force produced in response to motor command. In mice, motoneurone discharge is marked by the presence of sub-Threshold oscillations between action potentials which create a behavior of mixed mode oscillations (MMOs). These MMOs allow the motoneurones to fire at low frequency and are responsible for a sub-Primary range of discharge during which the firing frequency is irregular and the slope of current-Frequency relation is steep. We investigated the mechanisms responsible for these MMOs by in vivo recordings in anesthetized mice, using Dynamic Clamp, and by theoretical modelization in a monocompartimental model of motoneurone. Our results showed that MMOs were caused by sodium and potasium currents responsible for action potentials and that they emerged from a state of low membrane excitability caused by a slow inactivation of the sodium current. Paradoxically, we also showed that the after-Hyperpolarization current was able to increase the membrane excitability and to reduce MMOs by de-Inactivating the sodium current. Amyotrophic Lateral Sclerosis (ALS) leads to the specific degeneration of these motoneurones and is accompanied by a vacuolation of their dendritic trees. An early increase in motoneurons excitability during the disease has been widely proposed to account for their degeneration. Indeed, a motoneuron hyperexcitability of intrinsic or extrinsic origin could produce a deleterious excitotoxicity. If such a change of excitability is involved in the disease, it should last until the ages where the first denervation of neuromuscular junctions occurs. We recorded the electrophysiological properties of motoneurones in an in vivo preparation of adult SOD1-G93A mice, model of ALS. Our results showed that their input conductance was increased before the first denervation of their neuromuscular junctions. Nevertheless, their excitability was not modified. Far from being intrinsically hyperexcitable, a fraction of them even lost their ability to discharge repeatedly. We finally studied the vacuolation that takes place in dendrites of motoneurones during the disease and its relation with synaptic coverage. We have shown that the dendritic vacuolation takes place before the denervation and that the size of these vacuoles increases with age in SOD1-G93A mice. Interestingly, this increase was faster in the most vulnerable motoneurones. Although synaptic coverage was not altered in the disease, we ¬revealed higher densities of excitatory and inhibitory synapses on dendritic regions that vacuolate. These results suggest a link between synaptic activity and vacuoles formation in motoneurones during ALS. Motoneurones were not intrinsically hyperexcitable, instead, an excitotoxicity from a synaptic origin may be responsible for their degeneration

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49

Rajaraman, Swaminathan. "Micromachined three-dimensional electrode arrays for in-vitro and in-vivo electrogenic cellular networks." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28129.

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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Mark G. Allen; Committee Member: Elliot L. Chaikof; Committee Member: Ionnis (John) Papapolymerou; Committee Member: Maysam Ghovanloo; Committee Member: Oliver Brand.

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Nguyen, Thanh Hai. "Cibles sérotoninergiques et non sérotoninergiques des ISRS : approches Pharmacologique et Génétique in vivo chez la souris." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00663312.

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Les inhibiteurs sélectifs de recapture de la sérotonine (5-HT) (ISRS) bloquent directement le transporteur de la 5-HT (SERT) et stimulent indirectement de multiples auto- et hétérorécepteurs5-HT par l'augmentation de la concentration extracellulaire de 5-HT dans la fente synaptique. Cependant, le rôle des différents récepteurs ainsi que leur interaction dans les effets thérapeutiques des ISRS restent mal connus. Nous avons tenté de les identifier à l'aide de tests neurochimiques (microdialyse intracérébrale in vivo) et électrophysiologiques en utilisant une approche pharmacologique (utilisation de escitalopram, de ligands des récepteurs 5-HT1A/2A) et génétique (utilisation de souris knock-out [KO] SERT, 5-HT1A ou 5-HT2A). Les études neurochimiques et électrophysiologiques révèlent que les auto-(1A) et hétéro-(2A) récepteursagissent de concert pour maintenir une influence inhibitrice sur le système sérotoninergique, en particulier, en réponse au escitalopram : l'absence d'un récepteur est compensée par une régulation de l'autre. Enfin, les souris KO SERT constituent un nouveau modèle pour tester le mécanisme du escitalopram dans l'augmentation des concentrations de noradrénaline (NA).

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Dissertations / Theses on the topic 'In vivo electrophysiology recording'

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