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Academic literature on the topic 'Medial Entorhinal Cortex (MEC)'
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Dissertations / Theses on the topic "Medial Entorhinal Cortex (MEC)"
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Killian, Nathaniel J. "Bioelectrical dynamics of the entorhinal cortex." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/52148.
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The entorhinal cortex (EC) in the medial temporal lobe plays a critical role in memory formation and is implicated in several neurological diseases including temporal lobe epilepsy and Alzheimer’s disease. Despite the known importance of this brain region, little is known about the normal bioelectrical activity patterns of the EC in awake, behaving primates. In order to develop effective therapies for diseases affecting the EC, we must first understand its normal properties. To contribute to our understanding of the EC, I monitored the activity of individual neurons and populations of neurons in the EC of rhesus macaque monkeys during free-viewing of photographs using electrophysiological techniques. The results of these experiments help to explain how primates can form memories of, and navigate through, the visual world.
These experiments revealed neurons in the EC that represent visual space with triangular grid receptive fields and other neurons that prefer to fire near image borders. These properties are similar to those previously described in the rodent EC, but here the neuronal responses relate to viewing of remote space as opposed to representing the physical location of the animal. The representation of visual space may be aided by another EC neuron type that was discovered, free-viewing saccade direction cells, neurons that signaled the direction of upcoming saccades. Such a signal could be used by other cells to prepare to fire according to the future gaze location. Many of these spatially-responsive neurons also represented memory for images, suggesting that they may be useful for associating items with their locations.
I also examined the neuronal circuitry of recognition memory for visual stimuli in the EC, and I found that population synchronization within the gamma-band (30-140 Hz) in superficial layers of the EC was modulated by stimulus novelty, while the strength of memory formation modulated gamma-band synchronization in the deep layers and in layer III. Furthermore, the strength of connectivity in the gamma-band between different layers was correlated with the strength of memory formation, with deep to superficial power transfer being correlated with stronger memory formation and superficial to deep transfer correlated with weaker memory formation. These findings support several previous investigations of hippocampal-entorhinal connectivity in the rodent and advance our understanding of the functional circuitry of the medial temporal lobe memory system.
Finally, I explored the design of a device that could be used to investigate properties of brain tissue in vitro, potentially aiding in the development of treatments for disorders of the EC and other brain structures. We designed, fabricated, and validated a novel device for long-term maintenance of thick brain slices and 3-dimensional dissociated cell cultures on a perforated multi-electrode array. To date, most electrical recordings of thick tissue preparations have been performed by manually inserting electrode arrays. This work demonstrates a simple and effective solution to this problem by building a culture perfusion chamber around a planar perforated multi-electrode array. By making use of interstitial perfusion, the device maintained the thickness of tissue constructs and improved cellular survival as demonstrated by increased firing rates of perfused slices and 3-D cultures, compared to unperfused controls. To the best of our knowledge, this is the first thick tissue culture device to combine forced interstitial perfusion for long-term tissue maintenance and an integrated multi-electrode array for electrical recording and stimulation.
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Tennant, Sarah Anne. "Investigation of circuit mechanisms of spatial memory and navigation in virtual reality." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28915.
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Spatial memory and navigation relies on estimation of location. This can be achieved through several strategies, including the use of landmarks and by path integration. The latter involves inferring location from direction and distance moved relative to a known start point. The neural mechanisms of path integration are not well understood and implementation of experiments that dissociate path integration from alternative strategies is challenging. The roles of specific cell types are also unknown. Although grid cells in layer 2 of the medial entorhinal cortex (MEC) are theorised to be involved given their periodic and repeating firing fields that form a grid-like map that tiles the environment. Two excitatory cell populations have been identified in layer 2 of the MEC. Clusters of pyramidal cells that project to the CA1 are surrounded by dentate gyrus (DG) projecting stellate cells. Both populations have been shown to exhibit grid-like activity. The extent to which these cell types contribute to path integration or other strategies for solving spatial tasks is unknown. To investigate these issues, I developed a spatial memory task for mice, which uses virtual reality to generate sensitive measures of an animal’s ability to path integrate. In this task mice are trained to locate a reward zone marked with a visual cue within a virtual linear track. Use of path integration strategies can be tested in trials in which the reward zone is unmarked. In this task mice can locate the reward zone using either a local beaconing cue or path integration strategies. To assess whether self-motion derived motor information or visual feedback is used for path integration, I manipulated the translation between physical and virtual movement, putting optic and motor feedback in conflict. These manipulations suggest that mice use motor information to locate the reward zone on path integration trials. To test roles of stellate cells in the task I injected adeno-associated virus expressing the light chain of tetanus toxin, conditionally on the presence of Cre, into the MEC of mice expressing Cre specifically in stellate cells. This abolishes synaptic output from stellate cells therefore preventing them from influencing downstream neurons. I find mice with dorsal expression of the tetanus toxin virus in layer 2 stellate cells are unable to locate the reward zone using a local beaconing cue or path integration strategies. In contrast, mice with expression of green fluorescent protein (GFP) were able to locate the reward zone using both strategies. Locating the reward zone using path integration strategies first requires animal’s to learn the reward zone location, as denoted in trials with a beacon cue. To distinguish the role of stellate cells in learning versus execution of the tasks, I temporally modified the activity of stellate cells after mice had learnt to locate the reward zone using both strategies. Temporal control was achieved by use of cre-dependent adeno-associated viruses expressing mutant human muscarinic 4 receptor (hM4). When activated by clozapine - N - oxide (CNO), this receptor opens G-protein inwardly rectifying potassium (GIRK) channels and attenuates neuronal firing. Using this method, the activity of stellate cells can be temporally controlled during task execution and potentially distinguish their involvement in learning and execution of spatial memory tasks. No effect on behavioural performance was seen under these conditions. This may indicate stellate cells are required for learning but not execution of spatial memory tasks that require the use of local beaconing cues or path integration.
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Stensola, Tor. "Population codes in medial entorhinal cortex." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25419.
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Populasjonskoder i mediale entorhinal korteks Hjernebarken utfører kontinuerlig et velde av kompliserte funksjoner, hvis mekanismer vi kan tjene mye på å forstå. Nevrovitenskap er et relativt nytt fag, men med utrolig moment. Mye vites i dag om enkle nevroners egenskaper, men nevral komputering foregår i store trekk i interaksjonene mellom celler. Men på dette planet er det mange hindere som må overkommes; teknologisk nyvinning og konseptuell modning har ført til at nevrovitenskap gjennom de senere år har kunnet tilnærme seg spørsmal som fanger mekanismer på systemnivå. Hippokampus, som inneholder stedsselektive celler, utgjør et eksperimentelt system som tillater spørsmål om visse kjernemekanismer, slik som hukommelsesfunskjon og intern representasjonsdynamikk, uten streng ekpserimentell kontroll på innkommende og utgående signaler slik man baserer seg på i for eksempel sansenevrovitenskap. I hippokampusforskning er dyrets naturlige adferd en enorm ressurs. På grunn av den sterke tilknytningen til rom kan man ved å korrelere nevral aktivitet til dyrets adferd etablere svært robuste forhold mellom nevronenes aktivitet og funksjon på adferdnivå. Dette har ført til at hippokampusforskning har blitt en foregangsfront på innsamling av store datasett i dyr under normal adferd, samt tolkning av denne i adferdskontekst. Et stort skritt mot å forstå hvordan stedsselektiviteten i hippokampus oppstår og brukes kom med funnet av gitterceller, celler som er aktive i et gittermønster som dekker hele miljøet. Vi vet mye om disse cellenes oppførsel på enkeltcellenivå, men på grunn av teknisk krevende innspillingsteknikk har det vært vanskelig å spille inn nok celler til å forstå hvordan disse kombinerer til en populasjonskode for rom. Denne hindringen har vi nå overkommet, og i første arbeid brukte vi nye teknikker for å spille inn store antall gitterceller innen dyr og viser at gittercellekartet er organisert i moduler, hver med sin egen kartgeometri. Vi viser hvordan disse modulene er fordelt i vevet, og utviklet nye analyser for å beskive modulenes egenskaper. Vi viser at gitterkart i forskjellige moduler inad i dyr ikke bare kan innta forskjellig geometriske former, men også utføre separate operasjoner samtidig på samme eksperimentelle manipulering. Dette er første bevis på slik uavhengig funksjon i gitterkartet, og foreslår hvordan stedsceller kan generere høykapasitetslagring av representasjoner for forskjellige miljø. I andre arbeid beskriver vi hvordan en annen funksjonelt definert cellegruppe i entorhinal korteks fungerer på populasjonsnivå, denne gangen for celler som koder retning til dyret i forhold til miljøet. Vi viser at denne populasjonen har en topografisk fordeling langs samme akse i vevet som gitterceller utviser topografi, men at denne er kontinuerlig i motsetning til gitterkartets modulære fordeling. I siste arbeid viser vi at miljøets geometri bestemmer hvordan gitterkartet ankres til det eksterne rom. Vi beskriver en universal ankringsstrategi som er optimal for å skape størst mulig forskjell mellom populasjonskoder for områder langs rommets grenser. Dette brukes kanskje til å forhindre sanseforvirring av gitterkartet i miljø med geometrisk ambiguøse segmenter. Avhandlingen legger frem første beskrivelser av nevrale mekanismer på populasjonsnivå i entorhinal korteks, og gir flere innsikter i generell organisering av nettverkene som er involvert i stedssans og hukommelse<br>Current systems neuroscience has unprecedented momentum, in terms of both technological and conceptual development. It is crucial to study systems mechanisms and their associated functions with behavior in mind. Hippocampal and parahippocampal cortices has proved a highly suitable experimental system because the high level functions that are performed here, including episodic memory formation, are accessible through the clear readout of spatial behavior. Grid cells in medial entorhinal cortex (MEC) have been proposed to account for the spatial selectivity in downstream hippocampal place cells. Until now, however, entorhinal grid cells have only been studied on single cell– or small local ensemble level. The main reason for population studies lagging behind that of hippocampus is the technical difficulties associated with entorhinal implantation and recording. Here we have overcome some of the main technical hurdles, and recorded unprecedented number of cells from distinct functional classes in MEC. We show in Paper 1 that the entorhinal grid map is organized into sub-maps–or modules–that contain grid cells sharing numerous features including spatial pattern scale, orientation, deformation and temporal modulation. We also demonstrate that grid modules in the same system can operate independently on the same input, raising the possibility that hippocampal capacity for encoding distinct spatial representations is enabled by the grid input. We further show in Paper 2 that also head direction cells in entorhinal cortex distribute according to a functional topography along the dorsoventral axis. The head direction system, however, was not modular in contrast to the grid system. Finally, Paper 3 details a common grid anchoring strategy shared across animals and environments. The grid pattern displayed a striking tendency to align to the cardinal axes of the environment, but systematically offset 7.5°. Through simulations, we show that this constitutes an optimal orientation of the grid to maximally decorrelate population encoding of environment border segments, providing a possible link to border-selective cells in the mechanisms that embeds internal representation of space into external frames of reference. These findings have implications for our understanding of entorhinal and hippocampal computations and add several new venues for further investigation.
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Tang, Qiusong. "Structure function relationships in medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17163.
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In dieser Arbeit werden Struktur-Funktionsbeziehungen in der medialen entorhinalen Hirnrinde untersucht. Schicht 2 Neurone im medialen entorhinalen Cortex unterteilen sich in calbindin-positive Pyramidenzellen und calbindin-negative Sternzellen. Calbindin-positive Pyramidenzellen bündeln ihre apikalen Dendriten zusammen und formen Zellhaufen, die in einem hexagolen arrangiert sind. Das Gitter von calbindin-positiven Pyramidenzellhaufen ist an Schicht 1 Axonen und dem Parasubiculum ausgerichtet und wird durch cholinerge Eingänge innerviert. Calbindin-positive Pyramidenzellen zeigen stark theta-modulierte Aktivität. Sternzellen sind vertreut in der Schicht 2 angeordnet und zeigen nur schwach theta-modulierte Aktivität, ein Befund, der gegen eine Rolle von zell-intrinsischen Oszillationen in der Entstehung von Theta-Modulation spricht. In der Arbeit wurden Methoden entwickelt, um durch die juxtazelluläre Färbung und Identifikation von Zellen, die räumlichen Feuermuster von Schicht 2 Sternzellen und Pyramidenzellen zu bestimmen. Insbesondere wird gezeigt, dass die zeitlichen Feuermuster von Sternzellen und Pyramidenzellen so unterschiedlich sind, dass auch Daten von nichtidentifizierten extrazellulär abgeleiteten Zellen Sternzellen und Pyramidenzellen zugeordnet werden können. Die Ergebnisse zeigen, dass Gitterzell (engl. grid cell) Feuermuster relativ selten sind und in der Regel in Pyramidenzellen beobachtet werden. Grenzzell (engl. border cell) Feuermuster sind dagegen meistens in Sternzellen zu beobachten. Weiterhin wurde die Anatomie und Physiologie des Parasubiculums untersucht. Die Ergebnisse deuten auf die Existenz eines hexagonalen ‘Gitterzell-gitters’ in der entorhinalen Hirnrinde hin und sprechen für starke Struktur-Funktionsbeziehungen in diesem Teil der Hirnrinde.<br>Little is known about how medial entorhinal cortical microcircuits contribute to spatial navigation. Layer 2 principal neurons of medial entorhinal cortex divide into calbindin-positive pyramidal cells and dentate-gyrus-projecting calbindin-negative stellate cells. Calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum and cholinergic inputs. Calbindin-positive pyramidal cells were strongly theta modulated. Calbindin-negative stellate cells were distributed across layer 2 but avoided centers of calbindin-positive pyramidal patches, and were weakly theta modulated. We developed techniques for anatomical identification of single neurons recorded in trained rats engaged in exploratory behavior. Furthermore, we assigned unidentified juxtacellular and extracellular recordings based on spike phase locking to field potential theta. In layer 2 of medial entorhinal cortex, weakly hexagonal spatial discharges and head direction selectivity were observed in both cell types. Clear grid discharges were predominantly pyramidal cells. Border cells were mainly stellate neurons. Thus, weakly theta locked border responses occurred in stellate cells, whose dendrites sample large input territories, whereas strongly theta-locked grid discharges occurred in pyramidal cells, which sample small input territories in patches organized in a hexagonal ‘grid-cell-grid’. In addition, we investigated anatomical structures and neuronal discharge patterns of the parasubiculum. The parasubiculum is a primary target of medial septal inputs and parasubicular output preferentially targeted patches of calbindin-positive pyramidal cells in layer 2 of medial entorhinal cortex. Parasubicular cells were strongly theta modulated and carried mostly head-direction and border information, and might contribute to shape theta-rhythmicity and the (dorsoventral) integration of information across entorhinal grid scales.
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Ray, Saikat. "Functional architecture of the medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17595.
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Schicht 2 des mediale entorhinale Kortex (MEK) beinhaltet die größte Anzahl von Gitterzellen, welche durch ein hexagonales Aktivitätsmuster während räumlicher Exploration gekennzeichnet sind. In dieser Arbeit wurde gezeigt, dass spezielle Pyramidenzellen, die das Protein Calbindin exprimieren, in einem hexagonalen Gitter im Gehirn der Ratte angeordnet sind und cholinerg innerviert werden. Es ist bekannt, dass die cholinerge Innervation wichtig für die Aktivität von Gitterzellen ist. Weiterhin ergaben neuronale Ableitungen und Methoden zur Identifikaktion einzelner Neurone in frei verhaltenden Ratten, dass Calbindin-positive Pyramidenzellen (Calbindin+) eine große Anzahl von Gitterzellen beinhalten. Reelin-positive Sternzellen (Reelin+) im MEK, zeigten keine anatomische Periodizität und ihre Aktivität orientierte sich an den Begrenzungen der Umgebung. Eine weitere Studie untersucht die Architektur des MEK in verschiedenen Säugetieren, die von der Etrusker Spitzmaus, bis hin zum Menschen ~100 Millionen Jahre evolutionäre Vielfalt und ~20,000 fache Variation der Gehirngröße umfassen. Alle Arten zeigten jeweils eine periodische Anhäufung der Calbindin+ Zellen, was deren evolutive Bedeutung unterstreicht. Eine Studie zur Ontogenese der Calbindin Anhäufungen ergab, dass die periodische Struktur der Calbindin+ Zellen, sowie die verstreute Anordnung der Reelin+ Sternzellen schon zum Zeitpunkt der Geburt erkennbar war. Weitere Ergebnisse zeigen, dass Calbindin+ Zellen strukturell später ausreifen als Reelin+ Sternzellen - passend zu der Erkenntnis, dass Gitterzellen funktionell später reifen als Grenzzellen. Eine Untersuchung des Parasubiculums ergab, dass Verbindungen zum MEK präferiert in die Calbindin Anhäufungen in Schicht 2 projizieren. Zusammenfassend beschreibt diese Doktorarbeit eine Dichotomie von Struktur und Funktion in Schicht 2 des MEK, welche fundamental für das Verständnis von Gedächtnisbildung und deren zugrundeliegenden Mikroschaltkreisen ist.<br>The medial entorhinal cortex (MEC) is an important hub in the memory circuit in the brain. This thesis comprises of a group of studies which explores the architecture and microcircuits of the MEC. Layer 2 of MEC is home to grid cells, neurons which exhibit a hexagonal firing pattern during exploration of an open environment. The first study found that a group of pyramidal cells in layer 2 of the MEC, expressing the protein calbindin, were clustered in the rat brain. These patches were physically arranged in a hexagonal grid in the MEC and received preferential cholinergic-inputs which are known to be important for grid-cell activity. A combination of identified single-cell and extracellular recordings in freely behaving rats revealed that grid cells were mostly calbindin-positive pyramidal cells. Reelin-positive stellate cells in MEC were scattered throughout layer 2 and contributed mainly to the border cell population– neurons which fire at the borders of an environment. The next study explored the architecture of the MEC across evolution. Five mammalian species, spanning ~100 million years of evolutionary diversity and ~20,000 fold variation in brain size exhibited a conserved periodic layout of calbindin-patches in the MEC, underscoring their importance. An investigation of the ontogeny of the MEC in rats revealed that the periodic structure of the calbindin-patches and scattered layout of reelin-positive stellate cells was present around birth. Further, calbindin-positive pyramidal cells matured later in comparison to reelin-positive stellate cells mirroring the difference in functional maturation profiles of grid and border cells respectively. Inputs from the parasubiculum, selectively targeted calbindin-patches in the MEC indicating its role in shaping grid-cell function. In summary, the thesis uncovered a structure-function dichotomy of neurons in layer 2 of the MEC which is a fundamental aspect of understanding the microcircuits involved in memory formation.
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Wågen, Rine Sørlie. "Functional Dissection of Local Medial Entorhinal Cortex Subcircuit." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25537.
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The superficial layers of the medial entorhinal cortex(MEC) contain serval functionally specialized spatial cell types. suck a grid cells, head direction cells, border cells and cells with conjunctive properties. It is currently not know how the firing patterns of these vell populations map onto the architecture og the MEC circuit. Results from recent work suggest that there are two largely non-overlapping neuronal populations within superficial layers of MEC with different prosjecting targets. One of them target the hippocampus while the other prosjects extrahippocampally. It has been shown that all funtional MEC cell types prosject to the hippocampus, and a large part of these cells were grid cells. Based on these observations we wanted to investigate if there is a firrerence in fruntional cell distribution of MEC cells projecting to the contralateral MEC and cells prosjecting to hippocampus. Retrogradely transportable recombinant adeno-associated virus expressing Flag-tagged channelrhodopsin-2(ChR2), was injected in left MEC of 6 rats. This introduced optogenetic control over MEC neurons with direct årosjection to the contralateral MEC. Combining optogenetic and electrophysiological in vivo recordings, allowed identification of functional cell types with direct prosjection to the contralateral MEC, as these cells showed minimal response latencies to laser stimulations in the medial entorhinal cortex. We found border cells, head direction cells, non-spatial cells and interneurons with direct projection to the MEC, but no grid cells. This distrubution is in contrasts with the one found to project to the hippocampus, where grid cells are the predominant spatial cell type. More data are requred to determine if the sparsity of respnsive grid cells reflects limited sampling, or if the contralaterally--projecting cell population has distinct functional properties.
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Berndtsson, Christin H. "The Specificity of Output from Medial Entorhinal Cortex." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25538.
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The hippocampal formation(HF) and the parahippocampal region (PHR) have been implicated in learning and memory functions. These regions and their subregions form a highly interconnected and complex microcircuitry, where the entorhinal cortex consitutes the nodal point between the hippocampal formation and the cortex. The entorhinal cortex conssists of ywo functionally distinct subregions. It had been suggested that this diffrence in functional output results from differences in microcircuitry, and input and output characteristics whithin the regions. Therefore, in order to understand the function of the entorhinal cortex and how it contributes to the rest of the HF-PHR network, it is necessary to understand the microcircuity whitin the region. This study investigates the specificity of output from cell populations located in superficial layers of the medial entorhinal cortex. Fluorescent retrograde traces were injected into dorsal dentate gyrus(DG)and the dorsal medial enthorhinal cortex(MEC). Additional immunohistochemistry was performed in order to investigate the chemical markers for the retrogradely labelled cell populations. Labelled cells and possible colocalization of markers were analysedwith fluorescent microscopy. The results indicate the presence of a least three separate cell populations in superficial layers of MEC with different projection patterns and chemical markers. It remains to be seen how the cell populations described here relate to the functionally defined cell populations found in MEC.
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Schmidt-Helmstaedter, Helene. "Large-scale circuit reconstruction in medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19197.
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Es ist noch weitgehend ungeklärt, mittels welcher Mechanismen die elektrische Aktivität von Nervenzellpopulationen des Gehirns Verhalten ermöglicht. Die Orientierung im Raum ist eine Fähigkeit des Gehirns, für die im Säugetier der mediale entorhinale Teil der Großhirnrinde als entscheidende Struktur identifiziert wurde. Hier wurden Nervenzellen gefunden, die die Umgebung des Individuums in einer gitterartigen Anordnung repräsentieren. Die neuronalen Schaltkreise, welche diese geordnete Nervenzellaktivität im medialen entorhinalen Kortex (MEK) ermöglichen, sind noch wenig verstanden.
Die vorliegende Dissertation hat eine Klärung der zellulären Architektur und der neuronalen Schaltkreise in der zweiten Schicht des MEK der Ratte zum Ziel. Zunächst werden die Beiträge zur Entdeckung der hexagonal angeordneten zellulären Anhäufungen in Schicht 2 des MEK sowie zur Beschreibung der Dichotomie der Haupt-Nervenzelltypen dargestellt. Im zweiten Teil wird erstmalig eine konnektomische Analyse des MEK beschrieben. Die detaillierte Untersuchung der Architektur einzelner exzitatorischer Axone ergab das überraschende Ergebnis der präzisen Sortierung von Synapsen entlang axonaler Pfade. Die neuronalen Schaltkreise, in denen diese Neurone eingebettet sind, zeigten eine starke zeitliche Bevorzugung der hemmenden Neurone.
Die hier erhobenen Daten tragen zu einem detaillierteren Verständnis der neuronalen Schaltkreise im MEK bei. Sie enthalten die erste Beschreibung überraschend präziser axonaler synaptischer Ordnung im zerebralen Kortex der Säugetiere. Diese Schaltkreisarchitektur lässt einen Effekt auf die Weiterleitung synchroner elektrischer Populationsaktivität im MEK vermuten. In zukünftigen Studien muss insbesondere geklärt werden, ob es sich bei den hier berichteten Ergebnissen um eine Besonderheit des MEK oder ein generelles Verschaltungsprinzip der Hirnrinde des Säugetiers handelt.<br>The mechanisms by which the electrical activity of ensembles of neurons in the brain give rise to an individual’s behavior are still largely unknown. Navigation in space is one important capacity of the brain, for which the medial entorhinal cortex (MEC) is a pivotal structure in mammals. At the cellular level, neurons that represent the surrounding space in a grid-like fashion have been identified in MEC. These so-called grid cells are located predominantly in layer 2 (L2) of MEC. The detailed neuronal circuits underlying this unique activity pattern are still poorly understood.
This thesis comprises studies contributing to a mechanistic description of the synaptic architecture in rat MEC L2. First, this thesis describes the discovery of hexagonally arranged cell clusters and anatomical data on the dichotomy of the two principle cell types in L2 of the MEC. Then, the first connectomic study of the MEC is reported. An analysis of the axonal architecture of excitatory neurons revealed synaptic positional sorting along axons, integrated into precise microcircuits. These microcircuits were found to involve interneurons with a surprising degree of axonal specialization for effective and fast inhibition.
Together, these results contribute to a detailed understanding of the circuitry in MEC. They provide the first description of highly precise synaptic arrangements along axons in the cerebral cortex of mammals. The functional implications of these anatomical features were explored using numerical simulations, suggesting effects on the propagation of synchronous activity in L2 of the MEC. These findings motivate future investigations to clarify the contribution of precise synaptic architecture to computations underlying spatial navigation. Further studies are required to understand whether the reported synaptic specializations are specific for the MEC or represent a general wiring principle in the mammalian cortex.
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Heys, James Gerard. "Cellular mechanisms underlying spatial processing in medial entorhinal cortex." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12780.
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Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.<br>Functional brain recordings from several mammalian species including rodents, bats and humans demonstrate that neurons in the medial entorhinal cortex (mEC) represent space in a similar way. Single neurons in mEC, termed 'grid cells' (GCs), fire at regular repeating spatial intervals as the animal moves throughout the environment. In rodents, models GCs have been inspired by research that suggests a relationship between theta rhythmic electrophysiology in mEC and GC firing behavior. The h current time constant and frequency of membrane potential resonance (MPR) changes systematically along the dorsal to ventral axis of mEC, which correlates with systematic gradations in the spacing of the GC firing fields along the same anatomical axis. Despite significant efforts, the mechanism generating this periodic spatial representation remains an open question and the work presented in this thesis is directed towards answering this question
One major class of models that have been put forth to explain the grid pattern use interference between oscillations that are frequency modulated as a function of the animal's heading direction and running speed. Parts one and two of this thesis demonstrate how cholinergic modulation of MPR frequency could account for the expansion of grid field spacing that occurs during exploration of a novel environment. The result from these experiments demonstrate that activation of muscarinic acetylcholin receptors produces a decrease in the h current amplitude which causes a decrease in the MPR frequency.
Recently unit recordings have shown that GC firing pattern may exist in the mEC of the bat in the absence of these characteristic theta-rhythmic physiological mechanisms. The third section of the thesis details experiments in bat brain slices that were conducted to investigate the cellular physiology of principal neurons in layer II of mEC in the bat and directly test or intrinsic cellular mechanisms that could generate theta in mEC of the bat. Together this work reveals that significant h current is present in rodents and bats. However, the time course of the h current may differ between species such that theta band membrane potential resonance is present in the rodents but is not produced in bat neurons in mEC.
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D'Albis, Tiziano. "Models of spatial representation in the medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19306.
Full textAbstract:
Komplexe kognitive Funktionen wie Gedächtnisbildung, Navigation und Entscheidungsprozesse hängen von der Kommunikation zwischen Hippocampus und Neokortex ab. An der Schnittstelle dieser beiden Gehirnregionen liegt der entorhinale Kortex - ein Areal, das Neurone mit bemerkenswerten räumlichen Repräsentationen enthält: Gitterzellen. Gitterzellen sind Neurone, die abhängig von der Position eines Tieres in seiner Umgebung feuern und deren Feuerfelder ein dreieckiges Muster bilden. Man vermutet, dass Gitterzellen Navigation und räumliches Gedächtnis unterstützen, aber die Mechanismen, die diese Muster erzeugen, sind noch immer unbekannt. In dieser Dissertation untersuche ich mathematische Modelle neuronaler Schaltkreise, um die Entstehung, Weitervererbung und Verstärkung von Gitterzellaktivität zu erklären.
Zuerst konzentriere ich mich auf die Entstehung von Gittermustern. Ich folge der Idee, dass periodische Repräsentationen des Raumes durch Konkurrenz zwischen dauerhaft aktiven, räumlichen Inputs und der Tendenz eines Neurons, durchgängiges Feuern zu vermeiden, entstehen könnten. Aufbauend auf vorangegangenen theoretischen Arbeiten stelle ich ein Einzelzell-Modell vor, das gitterartige Aktivität allein durch räumlich-irreguläre Inputs, Feuerratenadaptation und Hebbsche synaptische Plastizität erzeugt.
Im zweiten Teil der Dissertation untersuche ich den Einfluss von Netzwerkdynamik auf das Gitter-Tuning. Ich zeige, dass Gittermuster zwischen neuronalen Populationen weitervererbt werden können und dass sowohl vorwärts gerichtete als auch rekurrente Verbindungen die Regelmäßigkeit von räumlichen Feuermustern verbessern können. Schließlich zeige ich, dass eine entsprechende Konnektivität, die diese Funktionen unterstützt, auf unüberwachte Weise entstehen könnte.
Insgesamt trägt diese Arbeit zu einem besseren Verständnis der Prinzipien der neuronalen Repräsentation des Raumes im medialen entorhinalen Kortex bei.<br>High-level cognitive abilities such as memory, navigation, and decision making rely on the communication between the hippocampal formation and the neocortex. At the interface between these two brain regions is the entorhinal cortex, a multimodal association area where neurons with remarkable representations of self-location have been discovered: the grid cells.
Grid cells are neurons that fire according to the position of an animal in its environment and whose firing fields form a periodic triangular pattern. Grid cells are thought to support animal's navigation and spatial memory, but the cellular mechanisms that generate their tuning are still unknown. In this thesis, I study computational models of neural circuits to explain the emergence, inheritance, and amplification of grid-cell activity.
In the first part of the thesis, I focus on the initial formation of grid-cell tuning. I embrace the idea that periodic representations of space could emerge via a competition between persistently-active spatial inputs and the reluctance of a neuron to fire for long stretches of time. Building upon previous theoretical work, I propose a single-cell model that generates grid-like activity solely form spatially-irregular inputs, spike-rate adaptation, and Hebbian synaptic plasticity.
In the second part of the thesis, I study the inheritance and amplification of grid-cell activity. Motivated by the architecture of entorhinal microcircuits, I investigate how feed-forward and recurrent connections affect grid-cell tuning. I show that grids can be inherited across neuronal populations, and that both feed-forward and recurrent connections can improve the regularity of spatial firing. Finally, I show that a connectivity supporting these functions could self-organize in an unsupervised manner.
Altogether, this thesis contributes to a better understanding of the principles governing the neuronal representation of space in the medial entorhinal cortex.