Academic literature on the topic 'Neural activity recording'

The study of neuronal and neurodegenerative diseases requires the development of new tools and technologies to create functional neuroelectronics allowing both stimulation and recording of cellular electrical activity. In the last decade organic electronics is digging its way in the field of bioelectronics and researchers started to develop neural interfaces based on organic semiconductors. The interest in such technologies arise from the intrinsic properties of organic materials such as low cost, transparency, softness and flexibility, as well the biocompatibility and the suitability in realizing all organic printed systems. In particular, organic field-effect transistor (OFET) -based biosensors integrate the sensing and signal amplification in a single device, paving the way to new implantable neural interfaces for in vivo applications. To master the sensing and amplification properties of the OFET-based sensors, it is mandatory to gain an intimate knowledge of the single transistors (without any analytes or cells) that cannot be limited to basic characterizations or to general models. Moreover, organic transistors are characterized by different working principles and properties as respect to their inorganic counterpart. We performed pulsed and transient characterization on different OFETs (both p-type and n-type) showing that, even though the transistors can switch on and off very fast, the accumulation and/or the depletion of the conductive channel continues for times as long as ten seconds. Such phenomenon must be carefully considered in the realization of a biosensor and in its applications, since the DC operative point of the device can drift during the recording of the cellular signals, thus altering the collected data. We further investigate such phenomenon by performing characterizations at different temperatures and by applying the deep level transient spectroscopy technique. We showed that the slow channel accumulation (and depletion) is due to the semiconductor density-of-states that must be occupied in order to bring the Fermi energy level close to the conduction band. This is a phenomenon that can takes several seconds and we described it by introducing a time-depend mobility. We also proposed a technique to estimate the behavior, in time, of the position of the Fermi energy level as respect to the conduction band. To understand the electrochemical transduction processes between living cell and organic biosensor, we realized two-electrodes structure (STACKs) where a drop of saline solution is put directly in contact with the organic semiconductor. On these devices, we performed electrochemical impedance spectroscopy at different DC polarizations and we developed an equivalent circuit model for the metal-organic semiconductor-solution structures that are typically used as transducers in biosensor devices. Our approach was extending the standard range of the bias voltages applied for devices that operate in water. This particular characterization protocol allowed to distinguish and investigate the different mechanisms that occur at the different layers and interfaces: adsorption of ions in the semiconductor; accumulation and charge exchange of carriers at the semiconductor/electrolyte interface; percolation of the ionic species through the organic semiconductor; ion diffusion across the electrolyte; ion adsorption and charge exchange at the platinum interface. We highlighted the presence of ion percolation through the organic semiconductor layer, which is described in the equivalent circuit model by means of a de Levie impedance. The presence of percolation has been demonstrated by environmental scanning electron microscopy and profilometry analysis. Although percolation is much more evident at high negative bias values, it is still present even at low bias conditions. In addition, we analyze two case studies of devices featuring NaCl (concentration of 0.1M) and MilliQ water as solution, showing that both cases can be considered as a particular case of the general model presented in this manuscript. The very good agreement between the model and the experimental data makes the model a valid tool for studying the transducing mechanisms between organic films and the physiological environment. Hence this model could be a useful tool not only for the characterization and failure analysis of electronic devices, such as water-gated transistors, electrophysiological interfaces, fuel cells, and others electrochemical systems, but also this model might be used in other applications, in which a solution is in intimate contact with another material to determine and quantify, if undesired mechanisms such as percolation and/or redox corrosive processes occur. Lastly, the knowledge gain on OFETs and STACKs were put together to realize electrolyte-gated field effect transistors (EGOFETs). We then developed a model to describes EGOFETs as neural interfaces. We showed that our model can be successfully applied to understand the behaviour of a more general class of devices, including both organic and inorganic transistors. We introduced the reference-less (RL-) EGOFET and we showed that it might be successfully used as a low cost and flexible neural interface for extracellular recording in vivo without the need of a reference electrode, making the implant less invasive and easier to use. The working principle underlying RL-EGOFETs involves self-polarization and back-gate stimulation, which we show experimentally to be feasible by means of a custom low-voltage high-speed acquisition board that was designed to emulate a real-time neuron response. Our results open the door to using and optimizing EGOFETs and RL-EGOFETs for neural interfaces.<br>Lo studio delle malattie neuronali e neuro-degenerative richiede lo sviluppo di nuovi strumenti e tecnologie per creare dispositivi neuro-elettronici funzionali che consentano sia la stimolazione che la registrazione dell'attività elettrica cellulare. Nell'ultimo decennio l'elettronica organica sta emergendo nel campo della bioelettronica e diversi gruppi di ricerca hanno iniziato a sviluppare interfacce neurali basate su semiconduttori organici. L'interesse per tali tecnologie deriva dalle proprietà intrinseche dei materiali organici quali basso costo, trasparenza, morbidezza e flessibilità, nonché la biocompatibilità e l'idoneità nella realizzazione di sistemi stampati completamente organici. In particolare, i biosensori basati sulla tecnologia a transistor ad effetto campo organico (OFET) integrano il sensing e l'amplificazione del segnale in un singolo dispositivo, aprendo la strada a nuove interfacce neurali impiantabili per applicazioni in vivo. Per padroneggiare le proprietà di rilevamento e amplificazione dei sensori basati su OFET, è obbligatorio acquisire una conoscenza approfondita dei singoli transistor (senza la presenza di analiti e/o cellule) che vadano oltre le caratterizzazioni di base o modelli generali. Inoltre, i transistor organici sono caratterizzati da diversi principi di funzionamento e diverse proprietà rispetto alla loro controparte inorganica. In questo lavoro abbiamo svolto caratterizzazioni impulsate e transienti su diversi OFET (sia di tipo p che di tipo n) mostrando che, anche se i transistor possono accendersi e spegnersi molto velocemente, l'accumulo e/o lo svuotamento del canale conduttivo continua per tempi che possono superare le decine di secondi. Tale fenomeno deve essere attentamente considerato nella realizzazione di un biosensore e nelle sue applicazioni, poiché il punto operativo DC del dispositivo può andare alla deriva durante la registrazione dei segnali cellulari, alterando così i dati raccolti. Questo fenomeno viene ulteriormente approfondito caratterizzano i dispositivi a diverse temperature e per mezzo della tecnica DLTS. Abbiamo dimostrato che il lento accumulo (e svuotamento) del canale è dovuto alla densità di stati del semiconduttore organico che devono poter essere occupati per portare il livello energetico di Fermi vicino alla banda di conduzione. Questo è un fenomeno che può richiedere diversi secondi che possiamo descrivere introducendo una mobilità dipendente dal tempo. Per comprendere i processi di trasduzione elettrochimica tra cellule viventi ed il biosensore organico, abbiamo realizzato una struttura a due elettrodi (STACK) in cui una goccia di soluzione salina viene messa direttamente a contatto con il semiconduttore organico. Su questi dispositivi, abbiamo eseguito la spettroscopia di impedenza elettrochimica a diverse polarizzazioni DC e abbiamo sviluppato un modello circuitale equivalente per le strutture metallo/semiconduttore organico/soluzione che vengono tipicamente utilizzate per la realizzazione di bio-trasduttori. Il nostro approccio prevede di estendere il range standard delle tensioni operative per questo genere di dispositivi. Ciò ha permesso di investigare e distinguere i diversi fenomeni che si verificano nei diversi strati e interfacce: adsorbimento di ioni nel semiconduttore; accumulo e scambio di cariche di portanti all'interfaccia semiconduttore/elettrolita; percolazione delle specie ioniche attraverso il semiconduttore organico; diffusione di ioni attraverso l'elettrolita; adsorbimento di ioni e scambio di carica all'interfaccia col metallo. Abbiamo evidenziato la presenza di percolazione ionica attraverso lo strato di semiconduttore organico, che è descritto nel modello circuitale per mezzo di un'impedenza di de Levie. La presenza di percolazione è stata dimostrata mediante microscopia elettronica a scansione ambientale e analisi profilometrica. Sebbene la percolazione sia molto più evidente a valori di bias negativi elevati, risulta presente anche a basse condizioni di bias. L'ottimo accordo tra il modello e i dati sperimentali rende il modello un valido strumento per studiare i meccanismi di trasduzione tra film organici e l'ambiente fisiologico. Quindi questo modello può essere uno strumento utile non solo per la caratterizzazione e l'analisi dei guasti dei dispositivi elettronici, come water-gated transistor, interfacce elettrofisiologiche, celle a combustibile e altri sistemi elettrochimici, ma anche nel caso in cui una soluzione è in intimo contatto con un altro materiale per determinare e/o quantificare se si verificano meccanismi indesiderati come percolazione e/o processi corrosivi. Infine, il bagaglio di conoscenze ottenuto studiando i dispositivi OFET e STACK è stato messo utillizato per realizzare dispositivi EGOFET. Abbiamo quindi sviluppato un modello per descrivere gli EGOFET come interfacce neurali. Abbiamo dimostrato che il nostro modello può essere applicato con successo per comprendere il comportamento di una classe più generale di dispositivi, compresi i transistor sia organici che inorganici. Abbiamo introdotto l'RL-EGOFET (reference-less EGOFET) e abbiamo dimostrato che questa struttura può essere utilizzata con successo come interfaccia neurale flessibile per il recording extracellulare in vivo senza la necessità di un elettrodo di riferimento, rendendo l'impianto meno invasivo e più facile da usare. I nostri risultati aprono la strada all'utilizzo e all'ottimizzazione di EGOFET e RL-EGOFET come interfacce neurali.

Throughout most of the 20th century the brain has been studied as a reflexive system with ever improving recording methods being applied within a variety of sensory and behavioural paradigms. Yet the brains of most animals (and all mammals) are spontaneously active with incoming sensory stimuli modulating rather than driving neural activity. The aim of this thesis is to characterize spontaneous neural activity across multiple temporal and spatial scales relying on biophysical simulations, experiments and analysis of recordings from the visual cortex of cats and dorsal cortex and thalamus of mouse. Biophysically detailed simulations yielded novel datasets for testing spike sorting algorithms which are critical for isolating single neuron activity. Sorting algorithms tested provided low error rates with operator skill being as important as sorting suite. Simulated datasets have similar characteristics to in vivo acquired data and ongoing larger-scope efforts are proposed for developing the next generation of spike sorting algorithms and extracellular probes. Single neuron spontaneous activity was correlated to dorsal cortex neural activity in mice. Spike-triggered-maps revealed that spontaneously firing cortical neurons were co-activated with homotopic and mono-synaptically connected cortical areas, whereas thalamic neurons co-activated with more diversely connected areas. Both bursting and tonic firing modes yielded similar maps and the time courses of spike-triggered-maps revealed distinct patterns suggesting such dynamics may constitute intrinsic single neuron properties. The mapping technique extends previous work to further link spontaneous neural activity across temporal and spatial scales and suggests additional avenues of investigation. Synchronized state cat visual and mouse sensory cortex electrophysiological recordings revealed that spontaneously occurring activity UP-state transitions fall into stereotyped classes of events that can be grouped. Single visual cortex neurons active during UP-state transitions fire in a partially preserved order extending previous findings on high firing rate neurons in rat somatosensory and auditory cortex. The firing order for many neurons changes over periods longer than 30-minutes suggesting a complex non-stationary temporal neural code may underlie spontaneous and stimulus evoked neural activity. This thesis shows that ongoing spontaneous brain activity contains substantial structure that can be used to further our understanding of brain function.<br>Medicine, Faculty of<br>Graduate

To discover general principles of biological sensorimotor control, insects have become remarkably successful model systems. In contrast to highly complex mammals, the functional organization of the insect nervous system in combination with a well-defined behavioural repertoire turned out to provide ideal conditions for quantitative studies into the neural control of behaviour. In addition, the search for biologically inspired control algorithms has further accelerated research into the neuronal mechanisms underlying flight and gaze stabilization, especially in blowflies. However, recording the neuronal activity in freely behaving insects, in particular in comparatively small insects such as blowflies, still imposes a major technical challenge. To date, electrophysiological recordings in unrestrained flies have never been achieved. This thesis describes the design and testing of a micro recording probe to be used for monitoring extracellular electrical activity in the nervous system of freely moving blowflies. In principle, this probe could also be used to study the neuronal control of behaviour in any other animal species the size of which is bigger than that of a blowfly. The nature of neuronal signals and the objective to record neuronal activity from behaving blowflies puts massive constraints on the specifications of the probe. I designed a differential amplifier with high gain, high linearity, low noise, and low power consumption. To fit the probe in the blowfly‟s head capsule and in direct contact with the animal‟s brain, the amplifier is on an unpackaged die. The neuronal signals are in the order of a few 100s of μV in amplitude. To be able to digitize such small signals >1000 times amplification is desirable. The small signal amplitudes also necessitate minimization of circuit noise. Linearity is necessary to prevent distortion of signal shape. Since connecting wires would impede movement of the animal, the probe would need to be powered by batteries. Therefore, low power is needed for two reasons: (i) to increase battery life, and therefore recording time, and (ii) because heat caused by power expenditure may damage the blowfly‟s brain or change its behaviour. To reduce power consumption I used CMOS transistors biased in the subthreshold region and a 2.2 V low power supply. The amplifier was characterized after fabrication by means of measuring its frequency response, linearity, and noise. I also recorded signals from a blowfly's brain and compared the performance of my recording probe with the performance of a high specification commercial amplifier in the time and frequency domains.