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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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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 hukommelseCurrent 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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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.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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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.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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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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Reifenstein, Eric. "Principles of local computation in the entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17625.
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Lebewesen sind jeden Tag Sequenzen von Ereignissen ausgesetzt, die sie sich merken wollen. Es ist jedoch ein allgemeines Problem, dass sich die Zeitskalen des Verhaltens und der Induzierung von neuronalem Lernen um mehrere Größenordnungen unterscheiden. Eine mögliche Lösung könnte "Phasenpräzession" sein - das graduelle Verschieben von Aktionspotential-Phasen relativ zur Theta-Oszillation im lokalen Feldpotential. Phasenpräzession ermöglicht es, Verhaltens-Sequenzen zeitlich zu komprimieren, herunter bis auf die Zeitskala von synaptischer Plastizität. In dieser Arbeit untersuche ich das Phasenpräzessions-Phänomen im medialen entorhinalen Kortex der Ratte. Ich entdecke, dass entorhinale Gitterzellen auf der für das Verhalten relevanten Einzellaufebene Phasenpräzession zeigen und dass die Phasenpräzession in Einzelläufen stärker ist als in zusammengefassten Daten vieler Läufe. Die Analyse von Einzelläufen zeigt zudem, dass Phasenpräzession (i) in Zellen aus allen Schichten des entorhinalen Kortex existiert und (ii) von den komplexen Bewegungsmustern der Ratten in zweidimensionalen Umgebungen abhängt. Zum Abschluss zeige ich, dass Phasenpräzession zelltyp-spezifisch ist: Sternzellen in Schicht II des medialen entorhinalen Kortex weisen klare Phasenpräzession auf, wohingegen Pyramidenzellen in der selben Schicht dies nicht tun. Diese Ergebnisse haben weitreichende Implikationen sowohl für das Lokalisieren des Ursprungs als auch für die m"oglichen Mechanismen von Phasenpräzession.Every day, animals are exposed to sequences of events that are worth recalling. It is a common problem, however, that the time scale of behavior and the time scale for the induction of neuronal learning differ by multiple orders of magnitude. One possible solution could be a phenomenon called "phase precession" - the gradual shift of spike phases with respect to the theta oscillation in the local field potential. Phase precession allows for the temporal compression of behavioral sequences of events to the time scale of synaptic plasticity. In this thesis, I investigate the phase-precession phenomenon in the medial entorhinal cortex of the rat. I find that entorhinal grid cells show phase precession at the behaviorally relevant single-trial level and that phase precession is stronger in single trials than in pooled-trial data. Single-trial analysis further revealed that phase precession (i) exists in cells across all layers of medial entorhinal cortex and (ii) is altered by the complex movement patterns of rats in two-dimensional environments. Finally, I show that phase precession is cell-type specific: stellate cells in layer II of the medial entorhinal cortex exhibit clear phase precession whereas pyramidal cells in the same layer do not. These results have broad implications for pinpointing the origin and possible mechanisms of phase precession.
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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.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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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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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.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.
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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.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.
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Kuruvilla, Maneesh. "The role of entorhinal cortex in processing environmental features." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/15597.
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The medial and lateral entorhinal cortices (MEC; LEC) are widely considered to provide spatial and non-spatial information respectively in the medial temporal lobe, particularly to the hippocampus. However, there is growing evidence to suggest that the functional differences between these two regions are not as clearly delineated as previously thought. This thesis aimed to assess if the two entorhinal sub-regions demonstrated a subtlety in encoding environmental features - landmarks and geometry – that are non-spatial in nature and yet provide an organism with relevant spatial information. In the first experiment, it was hypothesised that varying the scale of landmarks would result in the MEC and LEC encoding global and local spatial frameworks respectively. LEC lesioned animals showed deficits specifically in using a local spatial framework on a spatial memory task. This deficit was not related to processing individual local landmarks but rather the arrangement of cues as a whole. However, MEC lesions did not impair animals on successfully using either spatial framework. Experiment 2 attempted to glean an understanding of the MEC's role in processing environmental features, by investigating a condition where trapezoid geometry has been shown to play a role in distorting spatially modulated MEC grid cells. Rats trained on a distance estimation task demonstrated an overestimation and underestimation of distance when moving towards the converging and diverging ends of a trapezoid respectively, in line with predictions of grid cell function as a distance metric. Experiment 3 replicated the overestimation of distance with humans in a real-world trapezoid arena. Through lesion and behavioural results, this thesis finds evidence for the processing of local environmental features within entorhinal cortex. The LEC appears to use local landmarks to generate spatial frameworks while the MEC, via grid cells, encodes geometric information with implications for how organisms estimate distance in their environments.
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Gloveli, Tengis. "Die funktionelle Bedeutung von Projektionszellen des medialen entorhinalen Cortex in der Interaktion zwischen entorhinalem Cortex und Hippocampus." Doctoral thesis, [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=965714241.
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Klink, Ruby. "Functional organization and neuromodulation of entorhinal cortex layer II neurons." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42069.
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Morphological and electrophysical properties of layer II neurons from the medial entorhinal cortex were investigated in a rat brain slice preparation to enhance our understanding of the role the entorhinal cortex plays in the gating of afferent stimuli to the hippocampal formation.Morphological characterization revealed that layer II projection neurons fell into two distinct categories. 65% of neurons were identified as the stellate cells described previously. The remaining 35% had, for the most, a pyramidal-like morphology, and were referred to as non-stellates.
Electrophysiological characterization revealed that stellates and non-stellates had distinct electroresponsive properties. Notably, stellates, upon d.c. depolarization, generated subthreshold, sinusoidal-like, membrane potential oscillations at a mean frequency of 8.6 Hz and a 1-3 Hz repetitive bursting pattern, referred to as clustering. Non-stellates, when d.c. depolarized, never generated subthreshold oscillations nor spike clusters; instead they readily went into tonic firing.
Investigation of the main ionic mechanisms endowing stellates and non-stellates with their differential electroresponsiveness revealed that stellates exclusively possessed a fast, low threshold, Ba$ sp{2+}$-sensitive outward rectifier, which, in interplay with the persistent Na$ sp+$ conductance, generated the membrane potential oscillations.
The cholinergic agonist carbachol caused a depolarization in both stellates and non-stellates, associated with no change or a slight increase in apparent input resistance. In stellates, carbachol caused a decrease in the dominant frequency of the subthreshold membrane potential oscillations from 9.2 to 6.3 Hz. In non-stellates, carbachol transformed tonic firing into a slow voltage-dependent bursting discharge.
Investigation of the ionic mechanisms of the carbachol-induced depolarization in stellates and non-stellates revealed that it resulted mainly from activation of a Ca$ sp{2+}$ dependent cationic conductance largely carried by Na$ sp+$, mediated predominantly through m1 muscarinic receptor subtype activation.
Serotonin, in stellates, caused a variable response consisting of a hyperpolarization and/or depolarization, associated with a decrease in apparent input resistance, while in non-stellates, only the hyperpolarizing response was observed. In stellates, serotonin increased the frequency of subthreshold oscillations from 8.5 to 14.0 Hz. In non-stellates, serotonin did not affect spike-train adaptation nor the slow afterhyperpolarization following the train of spikes while it reduced both in stellates.
These results attest to the presence, in layer II of the medial entorhinal cortex, of two parallel information processing channels, both projecting to the hippocampal formation, and differentially modulated by the cholinergic and serotoninergic systems. One of these, the stellate channel, is endowed with robust rhythmic properties whose fundamental frequency can vary widely, depending on the relative tone of these two major neurotransmitter systems.
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Klink, Ruby. "Functional organization and neuromodulation of entorhinal cortex layer II neurons." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0014/NQ30311.pdf.
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Clasen, Sara Jean. "Arc Expression in the Entorhinal Cortex of the Behaving Animal." Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/146072.
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The hippocampus is a brain structure critical for learning and memory and receives a major input from the entorhinal cortex, which is itself divided into medial and lateral divisions. The medial division (MEC) contains grid cells, so named because the locations in space that increase any specific cell's ring rate are distributed as a triangular lattice-shaped grid [1]. The neurons of the lateral division (LEC) do not exhibit spatially selective firing [2], but may instead be involved in providing the hippocampus with information about the objects in the environment based on its anatomical connections with the perirhinal cortex [3]. The immediate-early gene Arc codes for a protein involved in synaptic plasticity and its expression is induced in principal cell populations by active behavior. In this experiment Arc is used to mark neuronal activation in LEC to test the hypothesis that these regions process different information about the rat's experience. Rats were trained to run on a circular track; on the day of the experiment, animals were divided into four groups: caged controls (negative control group); maximal electroconvulsive shock controls (positive control group); an A/A group which ran on a track populated with the same set of objects for two sessions separated by 20 minutes, and then sacrificed; and an A/B group which encountered two distinct sets of objects for each session. Arc expression was increased in the A/A and A/B groups relative to the caged controls; the pattern of Arc-labeled neuron proportions was altered in the A/B group relative to the A/A group, but no firm evidence of object-selective neurons was found. This may be due to low statistical power, sampling limitations, or unknown confounds.
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Chamberlain, Sophie. "Functional role of kainate receptors in the rat entorhinal cortex." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512314.
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Coutureau, Etienne. "Implication du cortex entorhinal dans l'inhibition latente chez le rat." Université Louis Pasteur (Strasbourg) (1971-2008), 1999. http://www.theses.fr/1999STR13010.
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Ce travail de recherche vise a preciser le substrat neurobiologique des operations elementaires de la cognition animale et en particulier celui de l'inhibition latente (il) chez le rat. L'il correspond a la diminution de reponse conditionnee resultant de la preexposition repetee et non renforcee du stimulus conditionnel avant son association avec le stimulus inconditionnel. Outre l'interet que ce phenomene represente dans l'etude des mecanismes de l'apprentissage, dans ses dimensions psychologiques et neurobiologiques, l'il est au centre d'un modele neuropsychologique de la schizophrenie. Il est en effet considere que le deficit d'il observable dans la schizophrenie de type i est coherent avec le niveau symptomatique, en particulier l'affaiblissement de l'influence des invariants memorises sur la perception courante. Chez l'animal, il est possible de mettre a l'epreuve le modele neuropsychologique en reproduisant certaines alterations structurales observees dans la pathologie (lesions). Dans ce cadre, notre travail a consiste a caracteriser les effets comportementaux et neurochimiques de la lesion du cortex entorhinal (ce), un composant de la formation hippocampique (fh). Une premiere etape de mon travail a consiste a etudier les effets sur l'il de lesions selectives (excitotoxiques) des differents composants de la fh. Contrairement aux predictions du modele, la lesion totale de l'hippocampe ou du subiculum n'a pas produit d'effet sur l'il alors que la lesion selective du ce a supprime l'effet de la preexposition, c'est a dire qu'elle a produit un deficit d'il. Nous avons par la suite montre que ce deficit : i) ne resulte pas de l'alteration de processus attentionnels mais plutot de celle de processus motivationnels consistant en une facilitation du conditionnement ii) ne semble pas lie a une augmentation de la transmission dopaminergique au sein du noyau accumbens, telle qu'appreciee d'une part, par les mesures indirectes d'activite locomotrice spontanee ou induite par l'amphetamine et d'autre part, par la mesure directe par microdialyse in vivo iii) peut etre restaure par l'administration d'un compose antipsychotique atypique (l'olanzapine) mais pas par celle d'un neuroleptique typique (l'haloperidol). Dans l'ensemble, nos resultats confirment la validite d'aspect et la validite theorique de l'il comme modele animal de schizophrenie, car des travaux recents montrent des alterations cytoarchitectoniques essentiellement au sein du ce chez les patients schizophrenes. Ces resultats permettent donc d'envisager l'etude du reseau neuronal implique non seulement dans le phenomene d'il mais aussi d'action des composes antipsychotiques.
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Comrie, Alison Emelie, and Alison Emelie Comrie. "Sparser Representation of Experience in Aged Rat Lateral Entorhinal Cortex." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/624949.
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The hippocampus undergoes biological changes with age that mediate memory
dysfunction. The hippocampus is highly connected to lateral entorhinal cortex (LEC), which is
thought to represent non-spatial features of experience, including odors. We aimed to discover if
LEC neuronal populations are selectively activated by distinct odors, and hypothesized that
aging alters these activity patterns. After training adult and aged rats to run laps around a track,
one behavioral group experienced two run sessions, 20 minutes apart, with the same set of
odors (AA) added around the track each time, while another group had distinct odor sets (AB).
mRNA of the immediate-early gene Arc is localized to discrete neuronal compartments based
on the time since activation. We used fluorescence in situ hybridization and confocal
microscopy to visualize the subcellular distribution of Arc mRNA to identify the neurons
activated during each session. The behavioral experiences induced elevated LEC activity, but
population activity failed to distinguish between distinct odor sets. This suggests that LEC
populations stably represent higher order features of experience. Additionally, a lower
proportion of LEC neurons participated during behavior in aged than in young rats. A decrease
in neuron activation could reflect a reduction or refinement of LEC network function.
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Garden, Derek Leonard Frank. "GABAergic transmission in the perirhinal cortex in vitro." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274770.
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Mena, Armando. "Electrophysiological and morphological characterization of medial entorhinal cortex layer III neurons." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=27379.
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The superficial layers of the entorhinal cortex (EC) are responsible for the transfer of neocortical input to the hippocampal formation (HPC) via the perforant path (PP). A significant, albeit not well characterized, component of the PP originates in EC layer III pyramidal cells and terminates directly in area CA1 of the HPC, circumventing the classical trisynaptic circuit. In an attempt to elaborate the input-output properties of this pathway, neurons of this layer were characterized both morphologically and electrophysiologically in an in vitro rat brain slice preparation using intracellular labeling and recording techniques with sharp micropipettes and under current-clamp conditions. These cells showed a typical pyramidal cell morphology. Analysis of the voltage-current relations demonstrated a rather linear membrane voltage behavior in the subthreshold range with the exception of pronounced inward rectification in the depolarizing direction due to a persistent Na$ sp+$-type current. This depolarizing current may provide the drive for the tonic discharge observed at rest in many of these neurons. Also, blockade of Ca$ sp{2+}$-conductances suggests that there is a high-threshold Ca$ sp{2+}$ component responsible for the shape of the spike, and indirectly responsible for both the spike AHP and the slow AHP following a train of spikes. The intrinsic electroresponsiveness of EC layer III pyramidal cells suggests that these neurons may perform a rather high-fidelity transfer function of incoming neocortical sensory information directly to the CA1 hippocampal subfield. This feedforward signal may function to gate the result of the information processing through entorhinal layer II and the trisynaptic pathway.
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Mena, Armando. "Electrophysiological and morphological characterization of medial entorhinal cortex layer III neurons." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0006/MQ29754.pdf.
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Pley-Bouverie, Barty. "Oscillatory communication between the rat hippocampus and entorhinal cortex in vivo." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540292.
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Kraus, Benjamin James. "Time and distance coding by the hippocampus and medical entorhinal cortex." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12801.
Full textAbstract:
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.Episodic memory, the ability to store and later recall individual experiences, plays a fundamental role in our day-to-day lives1 and reflects a temporal organization of events that form an experience. Numerous studies have shown that the hippocampus plays a crucial role in episodic memory. Recent studies have reported the existence of hippocampal "time cells", neurons that fire at particular moments during temporally extended periods when behavior and location are relatively constant. However, the origin of these hippocampal firing patterns, and the extent to which they are primarily determined by time, or instead by variations in behavior, location, or distance traveled over time, remains uncertain. Here we introduce a novel behavioral paradigm that allowed us to investigate firing patterns in the hippocampus and medial entorhinal cortex (MEC) as rats ran in place on a treadmill, thus "clamping" behavior and location while varying treadmill speed to distinguish time and distance traveled. We recorded activity in dorsal hippocampal CA1 and showed that "time cells" exist in this task and that their firing could not be explained by movement through space alone. Instead, we found that hippocampal neurons were heavily influenced by both time and distance, with different neurons reflecting these parameters to varying extents. These findings demonstrated that hippocampal neuronal networks capture the organization of time and distance in situations where these dimensions dominate an ongoing experience. We next recorded neural activity in the MEC a dominant source of input into the hippocampus, to determine whether the MEC is also involved in temporal processing. We found many MEC neurons exhibiting temporally-modulated firing that could not be explained by either movement through space or changes in head direction. This included neurons with single and multiple temporal firing fields, as well as neurons exhibiting temporally-periodic firing during treadmill running. In addition, we found that neurons classified as grid cells during open-field foraging often fired with one or more temporal firing fields during treadmill running. Together, these findings suggest that both hippocampal and MEC neurons code for temporal, as well as spatial and other environmental regularities.
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Parron, Carole. "Rôle du cortex entorhinal dans les comportements spatiaux chez le rat." Aix-Marseille 1, 2004. http://www.theses.fr/2004AIX11016.
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Le cortex entorhinal est un site de convergence multimodalitaire qui fournit la majorité des afférences hippocampiques en provenance des aires néocorticales. Les données de la littérature au sujet des effets de lésions du cortex entorhinal sont contradictoires et ne permettent pas de définir clairement le rôle joué par cette structure dans la mémoire spatiale. L'objectif de ce travail de recherche était de tester l'hypothèse selon laquelle le cortex entorhinal jouerait un rôle spécifique dans le traitement des informations spatiales. Nous avons pour cela entraîné des rats ayant des lésions du cortex entorhinal dans diverses tâches spatiales : navigation dans la piscine de Morris, réaction au changement spatial et non spatial au cours d'une tâche d'exploration d'objets, et tâche d'intégration des trajets. Nos résultats montrent que les rats ayant une lésion du cortex entorhinal sont déficitaires dans l'apprentissage d'une information spatiale dans une tâche de navigation, lorsqu'ils doivent utiliser des indices éloignés. En revanche, ils sont capables d'utiliser des indices proches pour apprendre à localiser un lieu. Les lésions du cortex entorhinal entraînent également des déficits dans la détection d'un changement dans une configuration d'objets, ainsi que dans la détection d'un nouvel objet. Enfin, les rats ayant une lésion du cortex entorhinal présentent des déficits dans une tâche d'intégration des trajets. L'ensemble de nos résultats suggère que le cortex entorhinal joue un rôle fondamental, distinct de celui de l'hippocampe et des aires néocorticales, dans la mémoire spatiale. Ces résultats sont compatibles avec l'idée que le cortex entorhinal jouerait un rôle d'intégrateur à plusieurs niveaux : intégration des informations spatiales allocentrées et égocentrées, et combinaison des informations spatiales et non spatiales. Ces processus pourraient être à l'origine de l'organisation et de la dynamique de la trace mnésique dans le système nerveuxThe entorhinal cortex has been described as the major structure that conveys cortical information to the hippocampus. Testing the effects of entorhinal cortical damage in spatial tasks has yielded contradictory results. The objective of the present work was to specify the function of the entorhinal cortex in spatial behaviors. Thus, we examined the effects of entorhinal cortical lesions in a variety of spatial tasks: place navigation in the Morris water maze, detection of spatial and non spatial changes during object exploration, and path integration. The results show that rats with lesions of the entorhinal cortex exhibited a place learning deficit when they had to use distal landmarks, but not when they had to use proximal landmarks. In addition, they were unable to detect a change in the spatial configuration of a set of objects or detect a novel object. Entorhinal-lesioned rats displayed also a path integration impairment. Overall, these results suggest that the entorhinal cortex plays an important role, distinct from that of the hippocampus or the neocortex, in the processing of spatial information. They are in agreement with the view that the entorhinal cortex is involved in the integration of allocentric and egocentric information as well as in the combination of spatial and non spatial information. These processes may be necessary for the organization of spatial memory in the brain
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Marozzi, E. C. "The cellular and molecular characterisation of context representation in entorhinal cortex." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1418414/.
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The hippocampus forms a representation of spatial context. Hippocampal place cells respond to contextual changes by “remapping”. Co-recorded place cells respond heterogeneously, with the majority responding in a conditional manner, whereby the response to one contextual cue (e.g. colour) is modulated by the presence of another (e.g. odour), suggesting contextual information is combined upstream. This thesis explored whether this combination occurs upstream in grid cells in medial entorhinal cortex. These cells have multiple receptive fields that span the environment in a triangular array and are thought to encode distance information. In Experiment 1, grid cells were recorded while rats explored geometrically equivalent boxes that differed only in their colour and odour. Results revealed grid cells remap to contextual changes via a translation but not a rotation of the grid fields. The majority of grid cells remapped conditionally, suggesting contextual cues are combined elsewhere. Unlike place cells, co-recorded grid cells responded in a homogeneous manner. Experiment 2 explored where colour and odour information is combined in the brain using two related phenomena. First, the time course of nuclear versus cytoplasmic Arc RNA accumulation is distinct, allowing neurons activated at two distinct time epochs to be visualised. Second, the decay of Arc, independent of electrophysiological activity, back to baseline levels after 2 hours in a familiar environment, known as electro-transcriptional decoupling (ETD), was also exploited. Animals were placed in boxes and experienced a colour change followed by an odour change (or vice versa). Arc activity was measured in the hippocampus and entorhinal cortex. Surprisingly results showed the time course of ETD was different in the hippocampus and entorhinal cortex than expected. Nevertheless, both structures were responsive to contextual changes compared to home cage controls. Overall, it is clear that the entorhinal cortex responds to non-spatial, contextual information, in additional to spatial information.
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Ramsden, Helen Lucy. "Mapping gene expression to function in adult mouse medial entorhinal cortex." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/8984.
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Deciphering the mechanisms that underlie circuit function in the hippocampal formation is a key challenge for neuroscience. This region, which includes the medial entorhinal cortex (MEC), is critical for spatial learning and episodic memory in humans. Spatially modulated cells in the MEC, the grid cells, provide a topographical representation of space, but we are yet to establish the neuronal properties that underlie this or the contribution that particular cells in different regions of the MEC and hippocampus make to circuit function. This is partially because the specific targeting of the network with genetic tools is complicated by a multitude of cell types with predominantly unknown molecular profiles. To address our limited understanding of the molecular organisation of the MEC, I have characterised how the expression of genes is distributed throughout different layers of the MEC, using a custom-designed resource that facilitates analysis of in situ hybridisation data from the Allen Brain Atlas. Through simultaneous extraction of gene expression data across thousands of 2D aligned images, I reveal striking differences between layers within MEC, demonstrating that layer II contains the highest proportion of genes enriched in a single layer, whereas gene expression is very rarely confined to layer III. Of particular interest, layer II of MEC is highly enriched for Alzheimer’s disease pathway genes, providing insight into its vulnerability as one of the first brain regions to show pathology. I also identify over 1000 genes that are expressed with a dorso-ventral gradient that maps onto the topographic organisation of MEC connectivity, grid cell spatial resolution and synaptic integrative properties of cells. An intriguing group of genes that closely relate circuit activity to gene expression, the plasticity-related activity-dependent genes, often show this pattern of expression. Focussing on the activity-dependent expression of one such activity-regulated, plasticity-related gene, Arc, I provide a novel view of MEC function. During simple novel exploration, Arc expression is up-regulated to a much greater extent in the deep layers of dorsal MEC than in the grid cell-rich superficial layers. By selectively disrupting the predominant hippocampal input to dorsal MEC, which terminates in the deep layers, I show that the significance of this up-regulation is independent of hippocampal inputs. Thus, although research addressing MEC function is particularly focussed on the superficial layers, during the exploratory behaviour that potentially primes the system for representing an environment, important plasticity may be occurring at the synapses onto deep layer neurons. In summary, my investigations of baseline and activity-dependent gene expression in MEC have revealed a molecular organisation both across different layers and along a functionally relevant gradient. This may be important for specifically targeting microcircuits in MEC and for characterising how laminar and regional differences contribute to the encoding of space in the hippocampal formation.
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Hamam, Bassam. "Functional organization of entorhinal cortex layer V neurons : electrophysiological and morphological characterization." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38488.
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The entorhinal cortex occupies an important anatomical position in the temporal lobe as the interface between the hippocampus and the neocortex. Its superficial cell layers funnel the cortical input into the hippocampus while the deep layer V is the major target of hippocampal output, which it then directs back to the cortex. This connectivity alone makes the entorhinal cortex a crucial element in what is known as the neocortical-hippocampal-neocortical circuit, a system involved in the long-term storage of "declarative" memories. However, the detailed analysis of the morphological and electrophysiological characteristics of cells in entorhinal cortex layer V had not been carried out, information that is necessary to understand how this cortical layer may participate in the processing of cortically directed hippocampal information. The main goal of the present study was thus to carry out by means of intracellular recording and labelling in a "in vitro" rat entorhinal cortex slice preparation an extensive characterization of the intrinsic electrophysiological characteristics of entorhinal cortex layer V principal neurons in correlation with their morphological attributes. Our main working hypothesis was that electrophysiologically, similar to the neocortex, layer V principal neurons in both the medial and lateral subdivisions of the entorhinal cortex would constitute a heterogeneous population comprised of regularly spiking cells and intrinsically bursting neurons.We found layer V of the entorhinal cortex to be comprised of three main cellular subtypes, pyramidal, horizontal and polymorphic neurons, that were electrophysiologically non-distinguishable. Cells in both medial and lateral entorhinal areas had similar morphological and electrophysiological properties. No intrinsically bursting neurons were encountered; instead, cells were classified as regular spiking neurons with varying spike-frequency adaptation. We also found that most layer V neurons displayed persistent Na+ current (INap) dependent subthreshold membrane potential oscillations; a mechanism that might endow layer V cells with a functional contribution to network rhythmicity.
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Stacey, Anne Elizabeth. "Modulation of GABA and glutamate release by neurokinins in the entorhinal cortex." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269259.
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Brandon, Mark Paul. "Theta oscillations and spatial coding in the presubsiculum and medial entorhinal cortex." Thesis, Boston University, 2011. https://hdl.handle.net/2144/34465.
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Thesis (Ph.D.)--Boston UniversityPLEASE 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.
2031-01-01
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Van, Cauter Tiffany. "Rôle du cortex entorhinal dans l'élaboration et le maintien des représentations spatiales." Aix-Marseille 1, 2008. http://www.theses.fr/2008AIX11078.
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La navigation spatiale chez le rat repose sur l'élaboration d'une représentation de l'environnement. L'hippocampe, caractérisé par la présence de cellules de lieu, est reconnu comme étant le support neuronal d'une telle représentation. Les cellules de lieu s'activent lorsque l'animal occupe une position spécifique dans l'espace et permettent de coder les caractéristiques d'un environnement donné. Situé à l'interface entre l'hippocampe et les aires corticales, le cortex entorhinal (CE), constitué du cortex entorhinal médian (CEM) et du cortex entorhinal latéral (CEL), est suceptible de jouer un rôle déterminant dans le fonctionnement hippocampique. La découverte récente des cellules grilles dans le CEM a conforté cette hypothèse. L'objectif des recherches réalisées au cours de cette thèse est donc d'examiner comment le CE contribue à l'élaboration et au maintien des représentations spatiales. Dans un premier temps, nous avons étudié les effets de lésions du CE sur l'activité des cellules de lieu et dans la mémorisation d'une configuration d'objets. Nos résultats montrent que les rats lésés sont, d'une part, perturbés pour réactiver la représentation d'un environnement familier et d'autre part, incapables de maintenir à court terme des informations nécessaires pour la mémorisation à long terme d'un nouvel environnement. Dans un second temps, nous avons examiné les rôles respectifs du CEL et du CEM dans la mémoire spatiale. Les effets de lésions du CEM ou du CEL dans deux tâches de mémoire spatiale montrent que le CEM est dédié au traitement des informations spatiales alors que le CEL traite préférentiellement des informations non spatiales, comme l'identité des objets. Dans une dernière étude, nous montrons que l'intégrité du système des cellules grilles du CEM est essentielle à la précision et la stabilité de la représentation spatiale des cellules de lieu. L'ensemble de ces résultats suggère que le CE, en interagissant avec l'hippocampe, est crucial à la mise en place et à la dynamique des représentations spatiales.
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WIRTH, SYLVIA. "Memoire olfactive a court-terme : modulation pharmacologique et role du cortex entorhinal." Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13039.
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Mon travail de these visait a etudier les processus neurobiologiques intervenant dans le controle du declin delai-dependant d'une trace mnesique. A cette fin, nous avons utilise une situation de reconnaissance olfactive spontanee chez le rat. Des effets promnesiants ont ete obtenus par l'administration systemique de fg 7142, une -carboline agoniste inverse partiel du recepteur aux benzodiazepines, ainsi que par l'administration chronique ou aigue d'egb 761, un extrait standardise de ginkgo biloba, ce chez des rats jeunes ou ages. A l'inverse, des effets amnesiants ont ete obtenus par l'administration intra-hippocampique de scopolamine, un antagoniste muscarinique de l'acetylcholine. Des experiences de lesions cerebrales ont permis de montrer que le cortex entorhinal excerce un controle de type inhibiteur, puisque sa lesion induit un effet promnesiant. Cet effet promnesiant semble etre specifique de la modalite olfactive, car d'autres taches n'ont pas ete facilitees par cette lesion. La lesion de structures voisines telles que le cortex perirhinal ou l'hippocampe n'ont en aucun cas, produit d'effets similaires a ceux de la lesion entorhinale : en effet, la lesion perirhinale s'est revelee depourvue d'effet dans l'ensemble des taches pratiquees ; la lesion de l'hippocampe n'a induit qu'une alteration minime de la reconnaissance olfactive et un deficit majeur dans la piscine de morris. La facilitation induite par la lesion entorhinale pourrait neanmoins faire intervenir des processus cholinergiques hippocampiques, puisque la microinjection de scopolamine dans cette structure a bloque cette facilitation. Dans leur ensemble, ces travaux suggerent que la lesion du cortex entorhinal se traduit par une profonde modification du mode de fonctionnement cerebral, sous-tendue par diverses alterations structurelles ou fonctionnelles au sein d'un reseau de structures qui restent a identifier.
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Barry, Caswell John. "Terra cognita : representations of space in the rodent hippocampus and entorhinal cortex." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444512/.
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The rodent hippocampus and associated structures are implicated in spatial memory and navigation. A necessary requirement of these roles is the ability to integrate incoming sensory information with pre-existing knowledge about an environment. With this dichotomy in mind, sensory control over place cell firing in the hippocampus, and grid cell firing in the entorhinal cortex were investigated. In the first experimental chapter a computational model of hippocampal place cell firing is presented. The model, a two layer feed-forwards network, describes place fields as a function of the distance and direction to boundaries surrounding an animal. It is shown that by incorporating the idea of boundaries with distinct sensory qualities, and by allowing synaptic weights to be updated by application of the BCM learning rule, the model is able to capture: (1) Experiential changes in place fields resulting from prolonged exposure to a static environment, and (2) Changes in place field position and firing rate induced by movement of cues and boundaries in a familiar environment. The model is shown to compare favourably with novel electrophysiological data collected for this purpose and with experimental findings published by other authors. The second experimental chapter investigates the affects geometric manipulations of a familiar environment have on the firing of medial entorhinal grid cells. Novel data is presented that shows grid cell firing represents an experience-dependent interaction between sensory input and learnt expectation about the size of an animal's enclosure. It is also shown that this interaction evolves with time to resolve conflict between the two sources of information. Finally it is noted that grids from a single animal are aligned and have fixed relative sizes. The final chapter discusses the data in terms of how the brain perceives and represents the world.
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Greenhill, Stuart David. "The role of synaptic noise in cortical excitability." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486807.
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The entorhinal cortex (EC) is a vital structure in the mammalian brain, implicated in the processes of learning and memory, and a possible site for the generation of seizures in temporal lobe epilepsy. Neurones in the EC are constantly bombarded with inhibitory and excitatory neurotransmitter. This background activity is thought to exert significant control on the excitability and function of neurones in cortical networks, with changes in the levels and proportion of background inhibition (IBg) and excitation (EBg) driving rhythmic oscillations in membrane potential, and even underlying the generation of epileptic seizures.
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Naumann, Robert Konrad. "Comparative areal and modular architecture of the cerebral cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2015. http://dx.doi.org/10.18452/17206.
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Die Neurone der Hirnrinde sind in Mikroschaltkreisen, Modulen und Arealen organisiert. In dieser Doktorarbeit habe ich die Neurobiologie und Hirnrindenstruktur der Etruskerspitzmaus - ein neues Modelltier für neurobiologische Forschung - und die modulare Struktur des entorhinalen Kortex der Ratte untersucht. Die geringe Größe des Gehirns der Etruskerspitzmaus bietet besondere Vorteile für das Verständnis kortikaler Aktivität von Zellgruppen. Die entorhinale Kortex enthält sowohl gut definierte funktionelle als auch anatomische Module und bietet daher eine einzigartige Gelegenheit für das Studium ihrer Wechselbeziehungen. Die Organisation der Hirnrinde der Etruskerspitzmaus reflektiert die Spezialisierung als schnelle, auf taktile Reize spezialisierte Jäger. Mehrere kortikale Regionen, die ein Drittel des kortikalen Volumens ausmachen, reagieren auf taktile Reize. Eine kortikale Hemisphäre enthält nur etwa eine Million Neuronen. Basierend auf der Zellarchitektur und histochemischen Färbungen haben wir 13 kortikale Regionen definiert - eine große Zahl angesichts der geringen Größe des Spitzmausgehirns. Pyramidenzellnester in Schicht 2 des medialen entorhinalen Kortex sind einfach zu identifizieren und eignen sich als Bezugssystem für die verschiedenen modulären Strukturen dieser Hirnregion. Diese Pyramidenzellen bündeln ihre Dendriten hin zu einem Punkt, der sich mit erhöhten Konzentrationen von präsynaptischen cholinergen Markern überschneidet. Cholinerge Transmission ist ein wichtiger Bestandteil des Theta-Rhythmus und unsere Ergebnisse zeigen, daß Pyramidenzellen im Vergleich zu Sternzellen doppelt so stark Theta-moduliert sind. Da fast alle Gitterzellen stark Theta-moduliert sind, ist anzunehmen dass Pyramidenzellen eine wichtige Rolle für die räumliche Navigation spielen. In dieser Arbeit wurden an der Hirnrinde der Etruskerspitzmaus sowie der entorhinalen Hirnrinde der Ratte modellhaft Struktur-Funktions-Beziehungen in der Großhirnrinde aufgeklärt.Neurons of the cerebral cortex are collectively organized into microcircuits, modules and cortical areas. Here, I study the neurobiology and cortical structure of the Etruscan shrew - a new model animal for neurobiological research - and the modular structure of the entorhinal cortex of the rat. The small size of the Etruscan shrew''s brain offers particular advantages for understanding cortical activity at the multi-cell level, due to its small number of cortical neurons and its intrinsic advantages for optical imaging approaches. The entorhinal cortex contains well-defined functional and anatomical modules and provides a unique opportunity for studying their interrelation. The organization of the cerebral cortex of the Etruscan shrew reflects their behavioral specialization as fast touch-and-kill hunters. Several cortical areas comprising a third of the cortical volume respond to vibrissal touch. One cortical hemisphere contains only about 1 million neurons. Cytoarchitecture and histochemical staining revealed 13 cortical regions - a large number considering the small size of the shrew''s brain. Pyramidal cell clusters in layer 2 of medial entorhinal are reliably identifiable and thus provide common anatomical framework for entorhinal cortex modularity. These cells form geometrically arranged clusters and bundle their dendrites towards a common point overlapping with presynaptic markers of cholinergic inputs. Cholinergic drive is an important component of theta-rhythmicity which we found to be two-fold stronger in pyramidal than in stellate neurons. Since nearly all grid cells are strongly theta modulated, we suggest that pyramidal cells may play an important role in microcircuits for spatial navigation. In this work, we studied the areal architecture of the Etruscan shrew cortex and the modular architecture of the rat medial entorhinal cortex as contributions towards understanding structure-function relations in the cerebral cortex.
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Lench, Alex. "Co-agonist regulation of pre and postsynaptic NMDA receptors in the entorhinal cortex." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678851.
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The NMDA receptor is a highly diverse receptor with many functions. In particular NMDA receptors present on postsynaptic spines mediate the effects of the synaptic neurotransmitter glutamate, whilst NMDA receptors present on presynaptic nerve terminals directly regulate the release of neurotransmitters. The aim of this thesis was to expand the characterisation of these two populations of NMDA receptors by examining the functional role of the co-agonist binding sites. NMDA receptors have been strongly implicated in mechanisms of cognition and also the pathophysiology epilepsy and so I have focused my study in the entorhinal cortex which is an area increasingly seen to be central to both of these phenomenon. Initial work focussed on the endogenous regulation of the presynaptic NMDA receptors. My results indicated that the co-agonist site of these receptors was activated by D-serine and that this ligand may come from astrocytes, in contrast to the observations that others have made for postsynaptic NMDA receptors. Following this, I then characterised the effects of partial agonists of the NMDA receptor co-agonist site at each of these populations of NMDA receptors and report differential effects for the function of these receptors. Finally I then examined the effects of the co-agonist site ligands on epileptiform activity as a simple form of emergent neuronal network activity. Results from my study of co-agonist site ligands provide important new insights into the relationship between NMDA receptors and neuronal synchrony and also the mechanism of cognitive enhancement by the high efficacy partial co-agonist D-Cycloserine.
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Solanka, Lukas. "Modelling microcircuits of grid cells and theta-nested gamma oscillations in the medial entorhinal cortex." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/10555.
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The relationship between structure, dynamics, and function of neural networks in nervous systems is still an open question in the neuroscience community. Nevertheless, for certain areas of the mammalian nervous system we do have sufficient data to impose constraints on the organisation of the network structure. One of these areas is the medial entorhinal cortex which contains cells with hexagonally repeating spatial receptive fields, called grid cells. Another intriguing property of entorhinal cortex and other cortical regions is a population oscillatory activity, with frequency in the theta (4-10 Hz) and gamma (30-100 Hz) range. This leads to a question, whether these oscillations are a common circuit mechanism that is functionally relevant and how the oscillatory activity interacts with the computation performed by grid cells. This thesis deals with applying the continuous attractor network theory to modelling of the microcircuit of layer II in the medial entorhinal cortex. Based on recent experimental evidence on connectivity between stellate cells, and fast spiking interneurons, I first develop a two-population spiking attractor network model that is capable of reproducing the activity of a population of grid cells in layer II. The network was implemented with exponential integrate and fire neurons that allowed me to address both the attractor states and the oscillatory activity in this region. Subsequently, I show that the network can produce theta-nested gamma oscillations with properties that are similar to the cross-frequency coupling observed in vivo and in vitro in entorhinal cortex, and that these theta-nested gamma oscillations can co-exist with grid-like receptive fields generated by the network. I also show that the connectivity inspired by anatomical evidence produces a number of directly testable predictions about the firing fields of interneurons in layer II of the medial entorhinal cortex. The excitatory-inhibitory attractor network, together with the theta-nested gamma oscillations, allowed me to explore potential relationships between nested gamma oscillations and grid field computations. I show, by varying the overall level of excitatory and inhibitory synaptic strengths, and levels of noise, in the network, that this relationship is complex, and not easily predictable. Specifically, I show that noise promotes generation of grid firing fields and theta-nested gamma oscillations by the model. I subsequently demonstrate that theta-nested gamma oscillations are dissociable from the grid field computations performed by the network. By changing the relative strengths of interactions between excitatory and inhibitory neurons in the network, the power and frequency of the gamma oscillations changes without disrupting the rate-coded grid field computations. Since grid cells have been suggested to be a part of the spatial cognitive circuit in the brain, these results have potential implications for several cognitive disorders, including autism and schizophrenia, as well as theories that propose a cognitive role for gamma oscillations.
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Rivest, Alexander Jay. "The Medial Entorhinal Cortex's role in temporal and working memory : characterization of a mouse lacking synaptic transmission in Medial Entorhinal Cortex Layer III." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/62719.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 190-212).
Declarative memory requires the integration and association of multiple input streams within the medial temporal lobe. Understanding the role each neuronal circuit and projection plays in learning and memory is essential to understanding how declarative and episodic-like memories are formed. This work here addresses the role of the medial entorhinal cortex layer III (MEC-III) to CA1 projections in episodic-like memory formation and recall. This circuit is addressed with a triple transgenic mouse which allows for the expression of tetanus toxin, an enzyme that disrupts synaptic vesicle fusion, specifically in MEC-III neurons. Utilizing this triple transgenic mouse model, which allows for the specific and reversible ablation of synaptic transmission only in medial entorhinal cortex layer III excitatory neurons, the function of this pathway in various learning and memory tasks is tested. Synaptic output from the medial entorhinal cortex layer III neurons is necessary for acquisition, but not recall of tone and contextual fear memories in trace fear conditioning, and not in delay conditioning. This is the first demonstration that acquisition and recall of the same memory engram do not require the exact same anatomy. Additionally, this pathway is necessary for performance in a delayed nonmatch-to-place working memory task, in which the animal must utilize memory from the previous trial to successfully complete the following trial. Both the trace and working memory paradigm require the integration of information across a delay, which we propose is supported by known persistent activity in entorhinal neurons. CAl receives input from both entorhinal layer III and CA3. We show that synaptic transmission from CA3 is not required for tone fear memory in the trace paradigm and not required for working memory in the same delayed nonmatch-to-place paradigm, further isolating the necessity for MEC-III inputs in both of these behaviors. Functional MEC-III synaptic transmission is also necessary for pattern-completion contextual recall in the pre-exposure contextual fear conditioning paradigm. Contrary to previous literature, the MEC-II to CAl pathway is not necessary for consolidation of spatial memories and anatomical tracings using this mouse line demonstrate that the MEC-III projects to CA1 and not CA3. The MEC-II pathway however, does project via two pathways to the same target in CA1, the perforant and alvear pathways. The alvear pathway has not been reported before in mice. Recent advances in mouse genetic tools have allowed for circuit studies of the medial temporal lobe. We have used these tools and elucidated some of the specific circuits involved with temporal and working memory.
by Alexander Jay Rivest.
Ph.D.
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Navratilova, Zaneta. "The Role of Path Integration on Neural Activity in Hippocampus and Medial Entorhinal Cortex." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/238892.
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This thesis explores the role of path integration on the firing of hippocampal place cells and medial entorhinal grid cells. Grid cells fire at equidistant locations in an environment, indicating that they keep track of the distance and direction an animal has moved in an environment. One class of model of path integration uses a continuous attractor network to update position information. The first part of this thesis showed that such a network can generate a "look-ahead" of neural activity that sweeps through the positions just visited and about to be visited, on the short time scale that is observed
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Schmidt-Helmstaedter, Helene [Verfasser], and Michael [Gutachter] Brecht. "Large-scale circuit reconstruction in medial entorhinal cortex / Helene Schmidt-Helmstaedter ; Gutachter: Michael Brecht." Berlin : Humboldt-Universität zu Berlin, 2018. http://d-nb.info/1185495282/34.
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Chenani, Alireza [Verfasser], and Christian [Akademischer Betreuer] Leibold. "Influence of medial entorhinal cortex on CA1 population bursts / Alireza Chenani ; Betreuer: Christian Leibold." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1176971743/34.
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Thompson, Sarah Elizabeth. "Control of glutamate andnGABA release by presynaptic GABAB receptors in the rat entorhinal cortex." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399850.
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Toleikyte, G. "Dendritic integration of synaptic inputs in the stellate cells of the medial entorhinal cortex." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1469417/.
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Grid cells fire action potentials at regular intervals in space, giving rise to a spectacularly regular and stable hexagonal arrangement of firing fields (Hafting et al., 2005). For this reason they have been proposed to represent a neural code for path integration (McNaughton et al., 2006). Grid cells have primarily been found in layer II of the medial entorhinal cortex (MEC) (Hafting et al., 2005). In this thesis I explore the dendritic properties of putative grid cells in MEC layer II and how they may contribute to generating the grid cell firing pattern. To assess the spatial and temporal dynamics of dendritic integration I have used patterned two-photon glutamate uncaging in vitro in combination with somatic whole cell recordings. My findings suggest that the principal neurons of MEC are highly excitable, exhibiting supralinear summation of near-simultaneous inputs and fast and slow dendritic spikes. Supralinear summation is timing-dependent and inputs are summated in a linear manner if separated by 8 ms time intervals. In order to understand the biophysical mechanisms of supralinear summation I blocked NMDA receptors and voltage-gated sodium channels (VGSCs) with D-AP5 and TTX respectively. Both supralinearity and dendritic spikes were abolished in the presence of both blockers, while TTX alone reduced supralinearity and abolished fast but not slow dendritic spikes. This suggests that fast dendritic spikes are largely mediated by VGSCs and slow dendritic spikes by NMDA receptors. Furthermore, I have assessed dendritic integration in physiologically relevant conditions by injecting current waveform to produce in vivo-like membrane potential dynamics, recorded when an animal was crossing a firing field of a MEC II principal neuron in a virtual environment (Schmidt-Hieber & Häusser, 2013). In vivo-like membrane potential dynamics increased supralinearity of the integral of EPSPs and probability of dendritic spikes. These findings have been integrated in a continuous attractor network model of grid cell firing by Christoph Schmidt-Hieber, to assess their relevance for the grid cell rate and temporal code, that revealed that supralinear dendritic integration increases grid cell rate code robustness and fast dendritic sodium spikes increase the precision of the temporal code (phase precession) of grid cells. To conclude, in this thesis I demonstrated that dendrites of principal neurons of MEC layer II integrate synaptic inputs in a highly supralinear manner, mediated by the VGSCs and NMDARs and boosted by putative dendritic spikes. Both supralinearity and proportion of dendritic spikes are increased under in vivo-like membrane potential dynamics. These findings suggest the hypothesis for the intracellular mechanisms that mediate the robustness of grid cell firing.
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Janác̆ková, Son̆a. "Functional maturation of postnatal hippocampus in rodents : electrophysiological approach." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T050.
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Les réseaux neuronaux, pendant leur période de développement, génèrent des patrons d’activité immatures qui sont supposés participer à la formation des circuits neuronaux. Ces activités synchronisées créent des conditions favorables pour la plasticité hebbienne qui soutient la formation des circuits locaux. Les travaux menés notamment sur les systèmes sensoriels ont montré que les circuits pauci-neuronaux locaux sont capables de présenter une activité synchrone tout en étant isolés du reste des structures cérébrales. La moelle épinière isolée produit des bursts qui sont à l’origine des secousses musculaires, la rétine insensible à la lumière génère des ondes d’activité, d’autres régions cérébrales génèrent des activités synchrones avant de remplir la fonction à laquelle ils sont destinés. De manière similaire, l’hippocampe du rat nouveau-né ou primate prématuré in vitro, ainsi que les néocortex immature in vitro, génèrent une activité neuronale synchronisée, appelée giant depolarising potentials (GDPs). En se basant uniquement sur ces études et en prenant en compte la maturation tardive de certaines projections neuronales à distance, il serait tentant de conclure que le cerveau immature fonctionne comme un ensemble de petits modules fonctionnels qui auto-entretiennent leur activité intrinsèque avant de se connecter entre eux pour créer un cerveau fonctionnel adulte. Cependant, certaines connexions à longue distance sont formées très tôt pendant le développement et permettent la propagation des oscillations immatures entre les structures connectées. En effet, les ondes rétinales se propagent au noyau géniculé latéral et ensuite jusqu’au cortex visuel ; les GDPs hippocampiques se propagent à l’hippocampe controlatéral, septum et cortex entorhinal et finalement, les secousses musculaires, en créant un feed-back sensoriel, déclenchent des oscillations gamma immatures ainsi que les spindle bursts dans le réseau thalamo-cortical. Un fonctionnement similaire est décrit chez le nouveau-né prématuré. Il paraît donc plus probable, que le cerveau soit, dès les stades précoces du développement, organisé en sous-systèmes fonctionnels reliés entre eux anatomiquement et fonctionnellement. Au sein des unités fonctionnelles sont générés des patrons d’activité immatures synchrones afin de créer des connexions organisées topographiquement qui serviront de base anatomique de la fonction finale. Si ces étapes développementales sont perturbées pendant les périodes critiques, le système ne pourra pas assurer sa fonction de manière adéquate au stade mature. L’hippocampe mature, ou plus exactement les circuits cortico-hippocampiques, jouant un rôle primordial dans la mémoire déclarative, l’orientation spatiale et l’inhibition du comportement. L’établissement de ces fonctions est progressif au cours du développement. Par exemple les adultes humains n’ont que rarement des souvenirs personnels datant avant l’âge de trois ans. Or, nous savons aujourd'hui que le bébé humain est capable de garder des souvenirs dans la mémoire déclarative (dépendante de l’hippocampe) au cours de la première année de vie avec une efficacité croissante, mais il ne se rappellera pas ces souvenirs à l’âge adulte (Bauer, 2006). Nous ne savons pas s’il s’agit d’un encodage différent d’emblée ou d’un processus secondaire supprimant l’accès à ces souvenirs précoces. Nous pouvons présumer qu’il existe des modifications des activités électrophysiologiques pendant le développement qui soutiennent la modification de ces fonctions. Au cours de ce travail de thèse, nous voulions savoir comment et à partir de quand l’hippocampe, qui reçoit des informations convergentes de nombreuses régions néocorticales, acquiert son mode de fonctionnement adulte. Afin de répondre à cette question nous avons étudié le système cortex entorhinal – hippocampe, le cortex entorhinal étant la principale entrée excitatrice de l’hippocampe et recevant des afférences de nombreuses régions du néocortex. (...)Neuronal networks spontaneously generate “immature” patterns of activity during development, which are thought to participate on the formation of neural circuits. Local neocortical as well as hippocampal circuits generate synchronised neuronal discharges providing support for Hebbian plasticity. Studies of sensory systems showed that local pauci-neuronal circuits were able to generate synchronous activity while isolated from other brain structures. Isolated spinal cord produces bursts evoking muscle twitching, light insensitive retina generates waves of activity, as well as other brain regions generate synchronous activities before fulfilling the function for which they are intended. Similarly, the hippocampus of newborn rat or premature primate in vitro, as well as immature neocortex in vitro, generates synchronised neuronal activity called giant depolarising potentials (GDPs). Based solely on these studies and taking into account the delayed maturation of certain long-distance neuronal projections, it would be tempting to conclude that the immature brain functions as a set of small functional modules that self-maintain their intrinsic activity before connecting together to create a functional adult brain. However, some long-distance connections are formed very early during development and allow the propagation of oscillations between immature connected structures. Indeed, retinal waves propagate to the lateral geniculate nucleus and then to the visual cortex, hippocampal GDPs propagate to the contralateral hippocampus, septum and entorhinal cortex, and finally, twitching, creating a sensory feedback, triggers immature gamma oscillations and spindle bursts in the thalamo-cortical network. A similar functioning is described in the premature newborn. It therefore seems more likely that the brain is, during the early stages of development, organised into functional subsystems interconnected anatomically and functionally. Within functional units are generated immature patterns of synchronous activity to create topographically organised connections that serve as anatomical basis of the final function. If these developmental stages are disturbed during critical periods, the system cannot perform its function adequately in mature stage. The mature hippocampus, or more precisely the cortico-hippocampal circuits, plays a key role in declarative memory, spatial organisation and behavioural inhibition. The establishment of these functions is progressive during development. For example, human adults rarely have personal memories dating before the age of three years. However, we now know that the human baby is able to keep memories in declarative memory (hippocampus-dependent) during the first year of life with increasing efficiency, but will not remember them in the adulthood. We do not know if the encoding of the memories is different or a secondary process inhibits the access to the early memories. We can assume that changes in electrophysiological activity during development support modification of these functions. In this thesis, we wanted to know how and from when the hippocampus, which receives convergent information from many cortical areas, acquires his adult mode of functioning. To answer this question we studied the entorhinal cortex-hippocampus system, entorhinal cortex being the main excitatory input to the hippocampus and receiving afferents from many parts of the neocortex. We were able to distinguish several periods in the development of the immature hippocampus: Period from P1 till P12 characterised by the sole presence of immature sharp waves triggered by the entorhinal cortex. Period from P13, when two types of sharp waves coexisted: the immature sharp waves and sharp waves as described in the adult animals newly emerged. The mature sharp waves, unlike the immature, can be accompanied by ripples. (...)
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De, Guzman Philip Henry. "Enhanced limbic network excitation in the pilocarpine animal model of temporal lobe epilepsy." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103376.
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Through the use of chronic experimental animal models, the majority of in vitro investigations of temporal lobe epilepsy have demonstrated enhanced network activity within the subdivisions of the hippocampal formation. However, clinical evidence in combination with in vivo and in vitro studies indicates that structures external to the hippocampus contribute to the genesis of seizure activity. To address the effects of limbic network excitation, I have utilized combined hippocampal---entorhinal cortex brain slices from pilocarpine-treated rats that display chronic seizures.My investigations have focused upon three structures, the subiculum, entorhinal cortex and the insular cortex. The experiments in the pilocarpine-treated subiculum demonstrated increased network excitability that was attributed to a more positive GABAA receptor mediated inhibitory post-synaptic potential (IPSP) reversal point coupled with a reduced IPSP peak conductance. Utilizing RT-PCR analysis and immunohistochemical staining we observed a decline in K+-Cl- cotransporter mRNA expression and a reduced number of parvalbumin-positive, presumptive inhibitory interneurons. My second project assessed the network hyperexcitability in layer V of the lateral entorhinal cortex. This is the first study to report spontaneous bursting, in the absence of epileptogenic agents, in the epileptic entorhinal cortex. We attributed this level of network excitation to reduced GABAA receptor mediated inhibition and increased synaptic sprouting. In the final project, we extended our slice preparation to include the insular cortex, a structure external to the temporal lobe. Our investigations identified a mechanism of NMDA receptor dependent synaptic bursting that masked GABA A receptor mediated conductances.
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Pastoll, Hugh. "Functional dissection of a cortical microcircuit for spatial computation." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7858.
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In mammals, spatial learning and memory depend on neural processing carried out in the hippocampal formation. Interestingly, extracellular recordings from behaving animals have shown that cells in this region exhibit spatially modulated activity patterns, thus providing insights into the neural activity underlying spatial behaviour. One area within the hippocampal formation, layer II of the medial entorhinal cortex, houses cells that encode a grid-like map of space using a firing rate code. At the same time, oscillatory signals at distinct theta (4–12 Hz) and gamma (30–120 Hz) frequencies are also present in layer II, providing a substrate for a timing code. To understand how layer II of the medial entorhinal cortex produces these outputs I sought to characterise the electrical properties and functional computational architecture of its microcircuitry. The functionality of any neural circuit depends on the electrical properties of its constituent cells. Because the grid cells in layer II are likely to be stellate cells, I used the perforated patch-clamp technique to accurately assess the intrinsic excitable properties of this cell type. Compared to whole-cell recordings, these recordings indicate that some intrinsic properties of stellate cells, such as spike clustering, which is revealed to be robust, are more likely to play a functional role in circuit computation. Conversely, other intrinsic properties, such as spontaneous membrane potential fluctuations, which are confirmed to be insufficiently stable to support reliable interference patterns, are revealed to be less likely than other, more robust electrical properties to play a direct role in circuit function. The characteristic connectivity profiles of different cell types are also critical for circuit function. To investigate cell type-specific connectivity in layer II I used optogenetic stimulation in combination with in vitro electrophysiology to record synaptic activity in different cell types while selectively activating distinct subpopulations of cells with light. Using this method I found that connections between stellate cells are absent or very rare and that communication between stellate cells is instead mediated by strong feedback inhibition from fast-spiking interneurons. Dissecting oscillatory activity in neural circuits may be important for establishing functionally relevant circuit architecture and dynamics but is difficult in vivo. I accomplished this in vitro by recapitulating the interacting theta and gamma rhythms that are observed in vivo with an optogenetic method. I found that locally driving a subset of neurons in the layer II microcircuit at theta frequency with a light stimiulus produced a nested field rhythm at gamma frequency that was also evident as rhythmic inhibition onto stellate cells. Critically, these interacting rhythms closely resembled those recorded from behaving animals. In addition, I found that this thetanested gamma is sufficiently regular to act as a clock-like reference signal, indicating its potential role in implementing a timing code. To functionally dissect the circuit I performed multiple simultaneous whole-cell patch-clamp recordings during circuit activation. These recordings revealed how feedback interactions between stellate cells and fast-spiking interneurons underpin the theta-nested gamma rhythm. Together, these results suggest that feedback inhibition in layer II acts as a common substrate for theta-nested gamma oscillations and possibly also grid firing fields, thereby providing a framework for understanding how computations are carried out in layer II of the medial entorhinal cortex.
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Yeh, Chia-Yu. "Cortical astroglial atrophy in ageing and Alzheimer's disease." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/cortical-astroglial-atrophy-in-ageing-and-alzheimers-disease(626eda4f-5713-4308-b8f9-7a89e51a9193).html.
Full textAbstract:
Ageing is a process correlated with cellular stress and increased risks of neurodegenerative diseases, in particular Alzheimer’s disease (AD), which is accompanied with severe cognitive and memory impairments. Both ageing and AD affect many brain regions and thus induce brain malfunctions. Among the brain regions, the entorhinal cortex (EC) has drawn more and more attentions due to its pivotal role in cognition and memory functions as well as its vulnerability to ageing process and AD neuropathology. Synaptic and neuronal degenerations, which are also manifest features of AD, occur in the EC during the ageing process and at the early stage of AD. In addition, both pathological hallmarks of AD, namely abnormal accumulation of β-amyloid (Aβ) and hyperphosphorlation of tau proteins, initially appear in the EC and then progress to other brain regions such as the hippocampus and the neocortex. Glial alterations in AD and ageing process have been considered as secondary event to neuronal changes. Nevertheless, accumulating evidence indicates the relevant and primary involvement of astroglia, which is responsible for brain homeostasis, in AD and ageing. In this thesis, we have focused on the astroglial alterations in the EC during the progression of AD in an animal model of the disease as well as in ageing process in non-transgenic control mice. We have used the triple transgenic mouse model of AD (3xTg-AD), which is the most relevant animal model of AD and resembles the spatiotemporal progression of human AD pathology. Our results revealed cytoskeletal atrophy of astrocytes in the EC of 3xTg-AD animals (Chapter 3), shown by significant decrease in GFAP surface and volume. This astroglial alteration began at very early age (1 month) and sustained till more advanced age (12 month). Moreover, Aβ plaques did not trigger astrogliosis, and there was rare presence of GFAP labelled astrocytes in the vicinity of Aβ deposition. This may reflect the relative indifference of astroglia in the EC and thus explain the susceptibility of the EC at the early stage of AD. To study whether astroglial atrophy in cytoskeleton compromise astrocytic function in glutamate homeostasis, we investigated the expression of glutamine synthetase (GS), which is specifically expressed in astrocytes and is critical for glutamate balance (Chapter 4). Our results showed constant GS expression and the density of GS positive astrocytes in the EC. However, dual labelling of GS and GFAP revealed 3 different subsets of astrocytes, being GS-, GFAP-, GS/GFAP- positive astrocytes. The morphology of GS-IR cells, measured by surface and volume, did not change in spite of the evident GFAP atrophy. Therefore, GFAP atrophy does not disturb glutamate homeostasis in the EC, suggesting diverse functional populations of astrocytes, which may show distinct responses during AD progression. In addition we also analysed astroglial changes during the ageing process in the EC and its major projection area, the hippocampus (Chapter 5). Astrocytes in the hippocampus exhibited prominent hypertrophy, shown by increased GFAP whereas entorhinal astrocytes in the EC had profound reduction in GFAP expression. This may implicate heterogeneous astrocytic responses to ageing in different brain regions. The general atrophy of astrocytes in the EC of 3xTg-AD mice and aged controls, suggests astroglial atrophy may results in reduced astrocytic coverage and modulation of synapses, accounting for the synaptic dysfunction in ageing and AD.
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Avsaar, Emin. "Actions of adenosine in the rat entorhinal cortex in an in vitro model of epilepsy." Thesis, Royal Holloway, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420817.
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Dhillon, Arvinder. "Short-term, frequency-dependent changes in synaptic transmission in the rat entorhinal cortex in vitro." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308860.
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Gauthier, Monique. "Traitement et mise en mémoire de l'information au niveau du cortex entorhinal chez la Souris." Grenoble 2 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb375978108.
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