Dissertations / Theses: 'Medial Entorhinal Cortex (MEC)'

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Killian, Nathaniel J. "Bioelectrical dynamics of the entorhinal cortex." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/52148.

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The entorhinal cortex (EC) in the medial temporal lobe plays a critical role in memory formation and is implicated in several neurological diseases including temporal lobe epilepsy and Alzheimer’s disease. Despite the known importance of this brain region, little is known about the normal bioelectrical activity patterns of the EC in awake, behaving primates. In order to develop effective therapies for diseases affecting the EC, we must first understand its normal properties. To contribute to our understanding of the EC, I monitored the activity of individual neurons and populations of neurons in the EC of rhesus macaque monkeys during free-viewing of photographs using electrophysiological techniques. The results of these experiments help to explain how primates can form memories of, and navigate through, the visual world. These experiments revealed neurons in the EC that represent visual space with triangular grid receptive fields and other neurons that prefer to fire near image borders. These properties are similar to those previously described in the rodent EC, but here the neuronal responses relate to viewing of remote space as opposed to representing the physical location of the animal. The representation of visual space may be aided by another EC neuron type that was discovered, free-viewing saccade direction cells, neurons that signaled the direction of upcoming saccades. Such a signal could be used by other cells to prepare to fire according to the future gaze location. Many of these spatially-responsive neurons also represented memory for images, suggesting that they may be useful for associating items with their locations. I also examined the neuronal circuitry of recognition memory for visual stimuli in the EC, and I found that population synchronization within the gamma-band (30-140 Hz) in superficial layers of the EC was modulated by stimulus novelty, while the strength of memory formation modulated gamma-band synchronization in the deep layers and in layer III. Furthermore, the strength of connectivity in the gamma-band between different layers was correlated with the strength of memory formation, with deep to superficial power transfer being correlated with stronger memory formation and superficial to deep transfer correlated with weaker memory formation. These findings support several previous investigations of hippocampal-entorhinal connectivity in the rodent and advance our understanding of the functional circuitry of the medial temporal lobe memory system. Finally, I explored the design of a device that could be used to investigate properties of brain tissue in vitro, potentially aiding in the development of treatments for disorders of the EC and other brain structures. We designed, fabricated, and validated a novel device for long-term maintenance of thick brain slices and 3-dimensional dissociated cell cultures on a perforated multi-electrode array. To date, most electrical recordings of thick tissue preparations have been performed by manually inserting electrode arrays. This work demonstrates a simple and effective solution to this problem by building a culture perfusion chamber around a planar perforated multi-electrode array. By making use of interstitial perfusion, the device maintained the thickness of tissue constructs and improved cellular survival as demonstrated by increased firing rates of perfused slices and 3-D cultures, compared to unperfused controls. To the best of our knowledge, this is the first thick tissue culture device to combine forced interstitial perfusion for long-term tissue maintenance and an integrated multi-electrode array for electrical recording and stimulation.

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Tennant, Sarah Anne. "Investigation of circuit mechanisms of spatial memory and navigation in virtual reality." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28915.

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Spatial memory and navigation relies on estimation of location. This can be achieved through several strategies, including the use of landmarks and by path integration. The latter involves inferring location from direction and distance moved relative to a known start point. The neural mechanisms of path integration are not well understood and implementation of experiments that dissociate path integration from alternative strategies is challenging. The roles of specific cell types are also unknown. Although grid cells in layer 2 of the medial entorhinal cortex (MEC) are theorised to be involved given their periodic and repeating firing fields that form a grid-like map that tiles the environment. Two excitatory cell populations have been identified in layer 2 of the MEC. Clusters of pyramidal cells that project to the CA1 are surrounded by dentate gyrus (DG) projecting stellate cells. Both populations have been shown to exhibit grid-like activity. The extent to which these cell types contribute to path integration or other strategies for solving spatial tasks is unknown. To investigate these issues, I developed a spatial memory task for mice, which uses virtual reality to generate sensitive measures of an animal’s ability to path integrate. In this task mice are trained to locate a reward zone marked with a visual cue within a virtual linear track. Use of path integration strategies can be tested in trials in which the reward zone is unmarked. In this task mice can locate the reward zone using either a local beaconing cue or path integration strategies. To assess whether self-motion derived motor information or visual feedback is used for path integration, I manipulated the translation between physical and virtual movement, putting optic and motor feedback in conflict. These manipulations suggest that mice use motor information to locate the reward zone on path integration trials. To test roles of stellate cells in the task I injected adeno-associated virus expressing the light chain of tetanus toxin, conditionally on the presence of Cre, into the MEC of mice expressing Cre specifically in stellate cells. This abolishes synaptic output from stellate cells therefore preventing them from influencing downstream neurons. I find mice with dorsal expression of the tetanus toxin virus in layer 2 stellate cells are unable to locate the reward zone using a local beaconing cue or path integration strategies. In contrast, mice with expression of green fluorescent protein (GFP) were able to locate the reward zone using both strategies. Locating the reward zone using path integration strategies first requires animal’s to learn the reward zone location, as denoted in trials with a beacon cue. To distinguish the role of stellate cells in learning versus execution of the tasks, I temporally modified the activity of stellate cells after mice had learnt to locate the reward zone using both strategies. Temporal control was achieved by use of cre-dependent adeno-associated viruses expressing mutant human muscarinic 4 receptor (hM4). When activated by clozapine - N - oxide (CNO), this receptor opens G-protein inwardly rectifying potassium (GIRK) channels and attenuates neuronal firing. Using this method, the activity of stellate cells can be temporally controlled during task execution and potentially distinguish their involvement in learning and execution of spatial memory tasks. No effect on behavioural performance was seen under these conditions. This may indicate stellate cells are required for learning but not execution of spatial memory tasks that require the use of local beaconing cues or path integration.

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Stensola, Tor. "Population codes in medial entorhinal cortex." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25419.

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Populasjonskoder i mediale entorhinal korteks Hjernebarken utfører kontinuerlig et velde av kompliserte funksjoner, hvis mekanismer vi kan tjene mye på å forstå. Nevrovitenskap er et relativt nytt fag, men med utrolig moment. Mye vites i dag om enkle nevroners egenskaper, men nevral komputering foregår i store trekk i interaksjonene mellom celler. Men på dette planet er det mange hindere som må overkommes; teknologisk nyvinning og konseptuell modning har ført til at nevrovitenskap gjennom de senere år har kunnet tilnærme seg spørsmal som fanger mekanismer på systemnivå. Hippokampus, som inneholder stedsselektive celler, utgjør et eksperimentelt system som tillater spørsmål om visse kjernemekanismer, slik som hukommelsesfunskjon og intern representasjonsdynamikk, uten streng ekpserimentell kontroll på innkommende og utgående signaler slik man baserer seg på i for eksempel sansenevrovitenskap. I hippokampusforskning er dyrets naturlige adferd en enorm ressurs. På grunn av den sterke tilknytningen til rom kan man ved å korrelere nevral aktivitet til dyrets adferd etablere svært robuste forhold mellom nevronenes aktivitet og funksjon på adferdnivå. Dette har ført til at hippokampusforskning har blitt en foregangsfront på innsamling av store datasett i dyr under normal adferd, samt tolkning av denne i adferdskontekst. Et stort skritt mot å forstå hvordan stedsselektiviteten i hippokampus oppstår og brukes kom med funnet av gitterceller, celler som er aktive i et gittermønster som dekker hele miljøet. Vi vet mye om disse cellenes oppførsel på enkeltcellenivå, men på grunn av teknisk krevende innspillingsteknikk har det vært vanskelig å spille inn nok celler til å forstå hvordan disse kombinerer til en populasjonskode for rom. Denne hindringen har vi nå overkommet, og i første arbeid brukte vi nye teknikker for å spille inn store antall gitterceller innen dyr og viser at gittercellekartet er organisert i moduler, hver med sin egen kartgeometri. Vi viser hvordan disse modulene er fordelt i vevet, og utviklet nye analyser for å beskive modulenes egenskaper. Vi viser at gitterkart i forskjellige moduler inad i dyr ikke bare kan innta forskjellig geometriske former, men også utføre separate operasjoner samtidig på samme eksperimentelle manipulering. Dette er første bevis på slik uavhengig funksjon i gitterkartet, og foreslår hvordan stedsceller kan generere høykapasitetslagring av representasjoner for forskjellige miljø. I andre arbeid beskriver vi hvordan en annen funksjonelt definert cellegruppe i entorhinal korteks fungerer på populasjonsnivå, denne gangen for celler som koder retning til dyret i forhold til miljøet. Vi viser at denne populasjonen har en topografisk fordeling langs samme akse i vevet som gitterceller utviser topografi, men at denne er kontinuerlig i motsetning til gitterkartets modulære fordeling. I siste arbeid viser vi at miljøets geometri bestemmer hvordan gitterkartet ankres til det eksterne rom. Vi beskriver en universal ankringsstrategi som er optimal for å skape størst mulig forskjell mellom populasjonskoder for områder langs rommets grenser. Dette brukes kanskje til å forhindre sanseforvirring av gitterkartet i miljø med geometrisk ambiguøse segmenter. Avhandlingen legger frem første beskrivelser av nevrale mekanismer på populasjonsnivå i entorhinal korteks, og gir flere innsikter i generell organisering av nettverkene som er involvert i stedssans og hukommelse Current systems neuroscience has unprecedented momentum, in terms of both technological and conceptual development. It is crucial to study systems mechanisms and their associated functions with behavior in mind. Hippocampal and parahippocampal cortices has proved a highly suitable experimental system because the high level functions that are performed here, including episodic memory formation, are accessible through the clear readout of spatial behavior. Grid cells in medial entorhinal cortex (MEC) have been proposed to account for the spatial selectivity in downstream hippocampal place cells. Until now, however, entorhinal grid cells have only been studied on single cell– or small local ensemble level. The main reason for population studies lagging behind that of hippocampus is the technical difficulties associated with entorhinal implantation and recording. Here we have overcome some of the main technical hurdles, and recorded unprecedented number of cells from distinct functional classes in MEC. We show in Paper 1 that the entorhinal grid map is organized into sub-maps–or modules–that contain grid cells sharing numerous features including spatial pattern scale, orientation, deformation and temporal modulation. We also demonstrate that grid modules in the same system can operate independently on the same input, raising the possibility that hippocampal capacity for encoding distinct spatial representations is enabled by the grid input. We further show in Paper 2 that also head direction cells in entorhinal cortex distribute according to a functional topography along the dorsoventral axis. The head direction system, however, was not modular in contrast to the grid system. Finally, Paper 3 details a common grid anchoring strategy shared across animals and environments. The grid pattern displayed a striking tendency to align to the cardinal axes of the environment, but systematically offset 7.5°. Through simulations, we show that this constitutes an optimal orientation of the grid to maximally decorrelate population encoding of environment border segments, providing a possible link to border-selective cells in the mechanisms that embeds internal representation of space into external frames of reference. These findings have implications for our understanding of entorhinal and hippocampal computations and add several new venues for further investigation.

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Tang, Qiusong. "Structure function relationships in medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17163.

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In dieser Arbeit werden Struktur-Funktionsbeziehungen in der medialen entorhinalen Hirnrinde untersucht. Schicht 2 Neurone im medialen entorhinalen Cortex unterteilen sich in calbindin-positive Pyramidenzellen und calbindin-negative Sternzellen. Calbindin-positive Pyramidenzellen bündeln ihre apikalen Dendriten zusammen und formen Zellhaufen, die in einem hexagolen arrangiert sind. Das Gitter von calbindin-positiven Pyramidenzellhaufen ist an Schicht 1 Axonen und dem Parasubiculum ausgerichtet und wird durch cholinerge Eingänge innerviert. Calbindin-positive Pyramidenzellen zeigen stark theta-modulierte Aktivität. Sternzellen sind vertreut in der Schicht 2 angeordnet und zeigen nur schwach theta-modulierte Aktivität, ein Befund, der gegen eine Rolle von zell-intrinsischen Oszillationen in der Entstehung von Theta-Modulation spricht. In der Arbeit wurden Methoden entwickelt, um durch die juxtazelluläre Färbung und Identifikation von Zellen, die räumlichen Feuermuster von Schicht 2 Sternzellen und Pyramidenzellen zu bestimmen. Insbesondere wird gezeigt, dass die zeitlichen Feuermuster von Sternzellen und Pyramidenzellen so unterschiedlich sind, dass auch Daten von nichtidentifizierten extrazellulär abgeleiteten Zellen Sternzellen und Pyramidenzellen zugeordnet werden können. Die Ergebnisse zeigen, dass Gitterzell (engl. grid cell) Feuermuster relativ selten sind und in der Regel in Pyramidenzellen beobachtet werden. Grenzzell (engl. border cell) Feuermuster sind dagegen meistens in Sternzellen zu beobachten. Weiterhin wurde die Anatomie und Physiologie des Parasubiculums untersucht. Die Ergebnisse deuten auf die Existenz eines hexagonalen ‘Gitterzell-gitters’ in der entorhinalen Hirnrinde hin und sprechen für starke Struktur-Funktionsbeziehungen in diesem Teil der Hirnrinde. Little is known about how medial entorhinal cortical microcircuits contribute to spatial navigation. Layer 2 principal neurons of medial entorhinal cortex divide into calbindin-positive pyramidal cells and dentate-gyrus-projecting calbindin-negative stellate cells. Calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum and cholinergic inputs. Calbindin-positive pyramidal cells were strongly theta modulated. Calbindin-negative stellate cells were distributed across layer 2 but avoided centers of calbindin-positive pyramidal patches, and were weakly theta modulated. We developed techniques for anatomical identification of single neurons recorded in trained rats engaged in exploratory behavior. Furthermore, we assigned unidentified juxtacellular and extracellular recordings based on spike phase locking to field potential theta. In layer 2 of medial entorhinal cortex, weakly hexagonal spatial discharges and head direction selectivity were observed in both cell types. Clear grid discharges were predominantly pyramidal cells. Border cells were mainly stellate neurons. Thus, weakly theta locked border responses occurred in stellate cells, whose dendrites sample large input territories, whereas strongly theta-locked grid discharges occurred in pyramidal cells, which sample small input territories in patches organized in a hexagonal ‘grid-cell-grid’. In addition, we investigated anatomical structures and neuronal discharge patterns of the parasubiculum. The parasubiculum is a primary target of medial septal inputs and parasubicular output preferentially targeted patches of calbindin-positive pyramidal cells in layer 2 of medial entorhinal cortex. Parasubicular cells were strongly theta modulated and carried mostly head-direction and border information, and might contribute to shape theta-rhythmicity and the (dorsoventral) integration of information across entorhinal grid scales.

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Ray, Saikat. "Functional architecture of the medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17595.

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Schicht 2 des mediale entorhinale Kortex (MEK) beinhaltet die größte Anzahl von Gitterzellen, welche durch ein hexagonales Aktivitätsmuster während räumlicher Exploration gekennzeichnet sind. In dieser Arbeit wurde gezeigt, dass spezielle Pyramidenzellen, die das Protein Calbindin exprimieren, in einem hexagonalen Gitter im Gehirn der Ratte angeordnet sind und cholinerg innerviert werden. Es ist bekannt, dass die cholinerge Innervation wichtig für die Aktivität von Gitterzellen ist. Weiterhin ergaben neuronale Ableitungen und Methoden zur Identifikaktion einzelner Neurone in frei verhaltenden Ratten, dass Calbindin-positive Pyramidenzellen (Calbindin+) eine große Anzahl von Gitterzellen beinhalten. Reelin-positive Sternzellen (Reelin+) im MEK, zeigten keine anatomische Periodizität und ihre Aktivität orientierte sich an den Begrenzungen der Umgebung. Eine weitere Studie untersucht die Architektur des MEK in verschiedenen Säugetieren, die von der Etrusker Spitzmaus, bis hin zum Menschen ~100 Millionen Jahre evolutionäre Vielfalt und ~20,000 fache Variation der Gehirngröße umfassen. Alle Arten zeigten jeweils eine periodische Anhäufung der Calbindin+ Zellen, was deren evolutive Bedeutung unterstreicht. Eine Studie zur Ontogenese der Calbindin Anhäufungen ergab, dass die periodische Struktur der Calbindin+ Zellen, sowie die verstreute Anordnung der Reelin+ Sternzellen schon zum Zeitpunkt der Geburt erkennbar war. Weitere Ergebnisse zeigen, dass Calbindin+ Zellen strukturell später ausreifen als Reelin+ Sternzellen - passend zu der Erkenntnis, dass Gitterzellen funktionell später reifen als Grenzzellen. Eine Untersuchung des Parasubiculums ergab, dass Verbindungen zum MEK präferiert in die Calbindin Anhäufungen in Schicht 2 projizieren. Zusammenfassend beschreibt diese Doktorarbeit eine Dichotomie von Struktur und Funktion in Schicht 2 des MEK, welche fundamental für das Verständnis von Gedächtnisbildung und deren zugrundeliegenden Mikroschaltkreisen ist. The medial entorhinal cortex (MEC) is an important hub in the memory circuit in the brain. This thesis comprises of a group of studies which explores the architecture and microcircuits of the MEC. Layer 2 of MEC is home to grid cells, neurons which exhibit a hexagonal firing pattern during exploration of an open environment. The first study found that a group of pyramidal cells in layer 2 of the MEC, expressing the protein calbindin, were clustered in the rat brain. These patches were physically arranged in a hexagonal grid in the MEC and received preferential cholinergic-inputs which are known to be important for grid-cell activity. A combination of identified single-cell and extracellular recordings in freely behaving rats revealed that grid cells were mostly calbindin-positive pyramidal cells. Reelin-positive stellate cells in MEC were scattered throughout layer 2 and contributed mainly to the border cell population– neurons which fire at the borders of an environment. The next study explored the architecture of the MEC across evolution. Five mammalian species, spanning ~100 million years of evolutionary diversity and ~20,000 fold variation in brain size exhibited a conserved periodic layout of calbindin-patches in the MEC, underscoring their importance. An investigation of the ontogeny of the MEC in rats revealed that the periodic structure of the calbindin-patches and scattered layout of reelin-positive stellate cells was present around birth. Further, calbindin-positive pyramidal cells matured later in comparison to reelin-positive stellate cells mirroring the difference in functional maturation profiles of grid and border cells respectively. Inputs from the parasubiculum, selectively targeted calbindin-patches in the MEC indicating its role in shaping grid-cell function. In summary, the thesis uncovered a structure-function dichotomy of neurons in layer 2 of the MEC which is a fundamental aspect of understanding the microcircuits involved in memory formation.

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Wågen, Rine Sørlie. "Functional Dissection of Local Medial Entorhinal Cortex Subcircuit." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25537.

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The superficial layers of the medial entorhinal cortex(MEC) contain serval functionally specialized spatial cell types. suck a grid cells, head direction cells, border cells and cells with conjunctive properties. It is currently not know how the firing patterns of these vell populations map onto the architecture og the MEC circuit. Results from recent work suggest that there are two largely non-overlapping neuronal populations within superficial layers of MEC with different prosjecting targets. One of them target the hippocampus while the other prosjects extrahippocampally. It has been shown that all funtional MEC cell types prosject to the hippocampus, and a large part of these cells were grid cells. Based on these observations we wanted to investigate if there is a firrerence in fruntional cell distribution of MEC cells projecting to the contralateral MEC and cells prosjecting to hippocampus. Retrogradely transportable recombinant adeno-associated virus expressing Flag-tagged channelrhodopsin-2(ChR2), was injected in left MEC of 6 rats. This introduced optogenetic control over MEC neurons with direct årosjection to the contralateral MEC. Combining optogenetic and electrophysiological in vivo recordings, allowed identification of functional cell types with direct prosjection to the contralateral MEC, as these cells showed minimal response latencies to laser stimulations in the medial entorhinal cortex. We found border cells, head direction cells, non-spatial cells and interneurons with direct projection to the MEC, but no grid cells. This distrubution is in contrasts with the one found to project to the hippocampus, where grid cells are the predominant spatial cell type. More data are requred to determine if the sparsity of respnsive grid cells reflects limited sampling, or if the contralaterally--projecting cell population has distinct functional properties.

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Berndtsson, Christin H. "The Specificity of Output from Medial Entorhinal Cortex." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25538.

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The hippocampal formation(HF) and the parahippocampal region (PHR) have been implicated in learning and memory functions. These regions and their subregions form a highly interconnected and complex microcircuitry, where the entorhinal cortex consitutes the nodal point between the hippocampal formation and the cortex. The entorhinal cortex conssists of ywo functionally distinct subregions. It had been suggested that this diffrence in functional output results from differences in microcircuitry, and input and output characteristics whithin the regions. Therefore, in order to understand the function of the entorhinal cortex and how it contributes to the rest of the HF-PHR network, it is necessary to understand the microcircuity whitin the region. This study investigates the specificity of output from cell populations located in superficial layers of the medial entorhinal cortex. Fluorescent retrograde traces were injected into dorsal dentate gyrus(DG)and the dorsal medial enthorhinal cortex(MEC). Additional immunohistochemistry was performed in order to investigate the chemical markers for the retrogradely labelled cell populations. Labelled cells and possible colocalization of markers were analysedwith fluorescent microscopy. The results indicate the presence of a least three separate cell populations in superficial layers of MEC with different projection patterns and chemical markers. It remains to be seen how the cell populations described here relate to the functionally defined cell populations found in MEC.

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Schmidt-Helmstaedter, Helene. "Large-scale circuit reconstruction in medial entorhinal cortex." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19197.

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Es ist noch weitgehend ungeklärt, mittels welcher Mechanismen die elektrische Aktivität von Nervenzellpopulationen des Gehirns Verhalten ermöglicht. Die Orientierung im Raum ist eine Fähigkeit des Gehirns, für die im Säugetier der mediale entorhinale Teil der Großhirnrinde als entscheidende Struktur identifiziert wurde. Hier wurden Nervenzellen gefunden, die die Umgebung des Individuums in einer gitterartigen Anordnung repräsentieren. Die neuronalen Schaltkreise, welche diese geordnete Nervenzellaktivität im medialen entorhinalen Kortex (MEK) ermöglichen, sind noch wenig verstanden. Die vorliegende Dissertation hat eine Klärung der zellulären Architektur und der neuronalen Schaltkreise in der zweiten Schicht des MEK der Ratte zum Ziel. Zunächst werden die Beiträge zur Entdeckung der hexagonal angeordneten zellulären Anhäufungen in Schicht 2 des MEK sowie zur Beschreibung der Dichotomie der Haupt-Nervenzelltypen dargestellt. Im zweiten Teil wird erstmalig eine konnektomische Analyse des MEK beschrieben. Die detaillierte Untersuchung der Architektur einzelner exzitatorischer Axone ergab das überraschende Ergebnis der präzisen Sortierung von Synapsen entlang axonaler Pfade. Die neuronalen Schaltkreise, in denen diese Neurone eingebettet sind, zeigten eine starke zeitliche Bevorzugung der hemmenden Neurone. Die hier erhobenen Daten tragen zu einem detaillierteren Verständnis der neuronalen Schaltkreise im MEK bei. Sie enthalten die erste Beschreibung überraschend präziser axonaler synaptischer Ordnung im zerebralen Kortex der Säugetiere. Diese Schaltkreisarchitektur lässt einen Effekt auf die Weiterleitung synchroner elektrischer Populationsaktivität im MEK vermuten. In zukünftigen Studien muss insbesondere geklärt werden, ob es sich bei den hier berichteten Ergebnissen um eine Besonderheit des MEK oder ein generelles Verschaltungsprinzip der Hirnrinde des Säugetiers handelt. The mechanisms by which the electrical activity of ensembles of neurons in the brain give rise to an individual’s behavior are still largely unknown. Navigation in space is one important capacity of the brain, for which the medial entorhinal cortex (MEC) is a pivotal structure in mammals. At the cellular level, neurons that represent the surrounding space in a grid-like fashion have been identified in MEC. These so-called grid cells are located predominantly in layer 2 (L2) of MEC. The detailed neuronal circuits underlying this unique activity pattern are still poorly understood. This thesis comprises studies contributing to a mechanistic description of the synaptic architecture in rat MEC L2. First, this thesis describes the discovery of hexagonally arranged cell clusters and anatomical data on the dichotomy of the two principle cell types in L2 of the MEC. Then, the first connectomic study of the MEC is reported. An analysis of the axonal architecture of excitatory neurons revealed synaptic positional sorting along axons, integrated into precise microcircuits. These microcircuits were found to involve interneurons with a surprising degree of axonal specialization for effective and fast inhibition. Together, these results contribute to a detailed understanding of the circuitry in MEC. They provide the first description of highly precise synaptic arrangements along axons in the cerebral cortex of mammals. The functional implications of these anatomical features were explored using numerical simulations, suggesting effects on the propagation of synchronous activity in L2 of the MEC. These findings motivate future investigations to clarify the contribution of precise synaptic architecture to computations underlying spatial navigation. Further studies are required to understand whether the reported synaptic specializations are specific for the MEC or represent a general wiring principle in the mammalian cortex.

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Heys, James Gerard. "Cellular mechanisms underlying spatial processing in medial entorhinal cortex." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12780.

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Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. 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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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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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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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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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 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. 2031-01-01

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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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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 [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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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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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<italic>in vivo</italic>. Adding intrinsic currents to the neurons in the network model allowed this look-ahead to recur every theta cycle, and generate grid fields of a size comparable to data. Grid cells are a major input the hippocampus, and are hypothesized to be the source of the place specificity of place cells. When an animal explores an open environment, place cells are active in a particular location regardless of the direction in which the animal travels through it. While performing a specific task, such as visiting specific locations in the environment in sequence, however, most place cells are active only in one direction. The second part of this thesis studied the development of this directionality. It was determined that upon the initial appearance of place fields in a novel environment, place cells fired in all directions, supporting the hypothesis that the path integration is the primary determinant of place specificity. The directionality of place fields developed gradually, possibly as a result of learning. Ideas about how this directionality could develop are explored.

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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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Tang, Qiusong [Verfasser], Michael [Akademischer Betreuer] Brecht, Richard [Akademischer Betreuer] Kempter, and Dietmar [Akademischer Betreuer] Schmitz. "Structure function relationships in medial entorhinal cortex / Qiusong Tang. Gutachter: Michael Brecht ; Richard Kempter ; Dietmar Schmitz." Berlin : Lebenswissenschaftliche Fakultät, 2015. http://d-nb.info/1068855606/34.

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Khawaja, Farhan A. "Ca²+-dependent K+ currents and spike-frequency adaptation in medial entorhinal cortex layer II stellate cells." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101151.

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We hypothesized that stellate cells (SCs) from layer II of the medial entorhinal cortex (MEC) may express currents that underlie spike-frequency adaptation (SFA) and that inhibitory modulation of these currents may permit the non-adapting nature of pulse-evoked post-burst after-discharges, a possible neuronal correlate of the post-stimulus delay firing seen in-vivo during working memory (WM) tasks. It was revealed that SCs contain medium (mIK(Ca)) and slow (sIAHP) Ca2+-dependent K+ currents. Furthermore, it was determined that mIK(Ca) is not mediated by apamin-sensitive SK channels in SCs, whereas it was found to be is apamin-sensitive in MEC layer II non-SCs. In addition, the results indicated that mIK(Ca) and sIAHP may underlie SFA in SCs and that mIK(Ca), sIAHP and SFA are subject to inhibitory modulation by PKA-activation. Therefore, PKA modulation may be important for SCs to exhibit post-burst after-discharges. Future work is required to determine whether PKA modulation of MEC layer II SCs plays an important role during WM tasks.

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Ray, Saikat [Verfasser], Michael [Gutachter] Brecht, Imre [Gutachter] Vida, and James [Gutachter] Poulet. "Functional architecture of the medial entorhinal cortex / Saikat Ray ; Gutachter: Michael Brecht, Imre Vida, James Poulet." Berlin : Lebenswissenschaftliche Fakultät, 2016. http://d-nb.info/1115767534/34.

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Shalinsky, Mark Howard. "Modulation of medial entorhinal cortex layer II neurons by two cation non-specific currents : IH and INCM." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84433.

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Neurons from layer II of the entorhinal cortex (EC} occupy a pivotal position in the medial temporal lobe gating the flow of neocortical information into the hippocampus. Previous "in vivo" studies had shown that EC layer II generates theta rhythmicity, and "in vitro" investigations have demonstrated that the main population of layer II projection neurons, the stellate cells, display intrinsic theta-like autopacemaker properties. EC layer II cells receive important subcortical serotoninergic and cholinergic input from the dorsal raphe and basal forebrain, respectively, and these inputs are known to affect the population oscillatory behaviour of cortical neurons, including the "theta" rhythm. Using pharmacological and voltage-clamp techniques in the EC slice preparation, the ionic mechanisms that contribute to the generation of intrinsic oscillations in the layer II stellate cells, and whether this mechanism was affected by serotoninergic neuromodulatory influences was investigated. As well, the aspects of how cholinergic muscarinic actions depolarize EC layer II neurons and may affect the oscillatory firing properties of these cells were also investigated. This Thesis confirmed that EC layer II stellate cells display a robust time-dependent inward rectification and demonstrated that this rectification is generated by a hyperpolarization activated non-specific inward cation current known as IH. I H, in conjunction with a low threshold persistent Na+ current was established to play a crucial role in the generation of the theta-like subthreshold oscillations. Next, similar to other cortical neurons, serotonin enhances IH by producing a small but significant positive shift in its activation curve. Finally, and with respect to cholinergic actions, the mechanism of cholinergic depolarization consists of both the block of a K+ conductance and, primarily, the activation of a noise non-specific cationic conductance, distinct from IH, named I NCM. I

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Toader, Oana-Daniela [Verfasser], and Hannah [Akademischer Betreuer] Monyer. "Genetic approaches to probe spatial coding in the medial entorhinal cortex / Oana-Daniela Toader ; Betreuer: Hannah Monyer." Heidelberg : Universitätsbibliothek Heidelberg, 2016. http://d-nb.info/1180736192/34.

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D'Albis, Tiziano [Verfasser], Richard [Gutachter] Kempter, Michael [Gutachter] Brecht, and Alessandro [Gutachter] Treves. "Models of spatial representation in the medial entorhinal cortex / Tiziano D'Albis ; Gutachter: Richard Kempter, Michael Brecht, Alessandro Treves." Berlin : Humboldt-Universität zu Berlin, 2018. http://d-nb.info/1185665161/34.

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Schlesiger, Magdalene I. [Verfasser], and Christian [Akademischer Betreuer] Leibold. "The role of the medial entorhinal cortex in spatial and temporal coding / Magdalene I. Schlesiger ; Betreuer: Christian Leibold." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1154385949/34.

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Schlesiger, Magdalene [Verfasser], and Christian [Akademischer Betreuer] Leibold. "The role of the medial entorhinal cortex in spatial and temporal coding / Magdalene I. Schlesiger ; Betreuer: Christian Leibold." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1154385949/34.

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Morgan, N. H. "The role of cannabinoid receptors in modulation of GABAergic neurotransmission in the rat medial entorhinal cortex in vitro." Thesis, Aston University, 2008. http://publications.aston.ac.uk/15356/.

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Type 1 cannabinoid receptors (CB1R) have a well established role in modulating GABAergic signalling with the central nervous system, and are thought to be the only type present at GABAergic presynaptic terminals. In the medial entorhinal cortex (mEC), some cortical layers show high levels of ongoing GABAergic signalling (namely layer II) while others show relatively low levels (layer V). Using whole-cell patch clamp techniques, I have, for the first time, demonstrated the presence of functional CB1R in both deep and superficial layers of the mEC. Furthermore, using a range of highly specific ligands for both CB1R and CB2R, I present strong pharmacological evidence for CB2Rs being present in both deep and superficial layers of the mEC in the adult rat brain. In brain slices taken at earlier points in CNS development (P8-12), I have shown that while both CB1R and CB2R specific ligands do modulate GABAergic signalling at early developmental stages, antagonists/ inverse agonists and full agonists have similar effects, and serve only to reduce GABAergic signalling. These data suggest that the full cannabinoid signalling mechanisms at this early stage in synaptogenesis are not yet in place. During these whole-cell studies, I have developed and refined a novel recording technique, using an amantidine derivative (IEM1460) which allows inhibitory postsynaptic currents to be recorded under conditions in which glutamate receptors are not blocked and network activity remains high. Finally I have shown that bath applied CB1 and CB2 receptor antagonists/ inverse agonists are capable of modulating kainic acid induced persistent oscillatory activity in mEC. Inverse agonists suppressed oscillatory activity in the superficial layers of the mEC while it was enhanced in the deeper layers. It seems likely that cannabinoid receptors modulate the inhibitory neuronal activity that underlies network oscillations.

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Carmichael, James Eric Sørensen. "The Effects of Speed and Acceleration on the Theta and Delta Band Oscillations in the Hippocampus and Medial Entorhinal Cortex." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-17085.

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The theta band oscillation in the hippocampus and medial entorhinal cortex carries a strong correlation with free movement throughout an environment. Recently several models of these oscillations and their relationship to spatially modulated cells in the hippocampus and entorhinal cortex have started to emerge. One area of focus in theta research has been how the speed of movement modulates the theta frequency. Previous attempts to determine this relationship in the hippocampus and medial temporal lobe have failed to either engage the subject in prolonged running at a constant velocity, or they have not been able to facilitate natural movements during the recordings. Using a novel apparatus that can provide strict control over the speed of a freely moving rat, this study examines the relationship between movement related variables such as running speed and acceleration and oscillations in the theta (7-12Hz) and delta (1.5-6Hz) band in the medial entorhinal cortex and hippocampus during both constant running and during transitions in speed. The results showed that there was no relationship between running speed and medial entorhinal theta oscillations, as had previously been reported in the open field experiments. Interestingly the modulation of hippocampal and entorhinal theta was related to the magnitude of the acceleration of the animals’ movements. This novel finding questions the current opinion attained from open field recordings of instantaneous constant running as well as the models of grid cell firing and theta phase precession that assume a linear relationship between running speed and theta frequency.

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Fischer, Caroline [Verfasser], and Andreas [Akademischer Betreuer] Herz. "Biophysical foundation and function of depolarizing afterpotentials in principal cells of the medial entorhinal cortex / Caroline Fischer ; Betreuer: Andreas Herz." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1196529035/34.

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Topczewska, Aleksandra Paulina. "The role of Cav3.2 Ca2+ channels in influencing the activity of the layer II stellate cells of the Medial Entorhinal Cortex." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10042158/.

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Layer II (L II) Medial Entorhinal Cortex (MEC) stellate cell (SC) intrinsic membrane properties vary along the MEC dorsal-ventral axis. This has been attributed partly to altered HCN and K+ conductances (Garden et al. 2008; Giocomo and Hasselmo 2008). The subthreshold active T-type CaV3.2 Ca2+ channels, though, are also expressed in the MEC (Huang et al. 2011). CaV3.2 channels are known to influence neuronal excitability but their effects on dorsal and ventral LII MEC SC properties remain unknown. To investigate this, I obtained acute brain slices from CaV3.2 wild type (CaV3.2+/+) and null (CaV3.2-/-) 5-8 week old mice and made electrophysiological recordings from dorsal and ventral L II MEC SC. CaV3.2-/- ventral neurons displayed significantly reduced input resistance but little difference in resting membrane potential (RMP) compared with CaV3.2+/+ ventral neurons. Consequently, depolarizing steps resulted in fewer action potentials in CaV3.2-/- ventral SC than in wild type neurons. In contrast, dorsal CaV3.2-/- and CaV3.2+/+ SC properties were similar. Furthermore, CaV3.2+/+ ventral cells had a significantly higher α excitatory post synaptic potentials (αEPSP) summation ratio (at 50 Hz) in comparison to CaV3.2-/- ventral neurons. The Cav3 inhibitors, NiCl2 and TTA-P2, also significantly reduced input resistance and action potential firing in CaV3.2+/+ ventral neurons, whilst having little effect on CaV3.2+/+ dorsal or CaV3.2-/- neurons. Furthermore, voltage-clamp experiments revealed a significantly greater T-type Cav3.2 Ca2+ current in ventral than dorsal neurons. Our results suggest that Cav3.2 channels selectively affect L II MEC ventral SC properties, thereby contributing to the intrinsic membrane gradient across the MEC dorsal-ventral axis.

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Bladon, John H. "The medial and lateral entorhinal cortex of the rat represent item and context with overlap in a context cued object discrimination paradigm." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12056.

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Thesis (M.A.)--Boston University The entorhinal cortex is the main input to the hippocampus and is crucial for episodic memory. The medial entorhinal cortex (MEC) is distinct from the lateral entorhinal cortex (LEC) in that the former processes spatial information, whereas the lateral is implicated in processing objects. However, there is significant overlap in function between the two areas. The spatial representation in the MEC is modulated by behavioral contingencies. Similarly, the LEC shows spatial modulation in the presence of objects. It is clear that the MEC and LEC share some but not all mnemonic and navigational functions. To better understand the mnemonic functions of the entorhinal cortex, this study monitored single unit activity with both the MEC and LEC of the rat during a context cued object discrimination task. In short, the rat was rewarded by choosing object X over object Y in context A and object Y over object X in context B regardless of position within each context. It was hypothesized that cells in the MEC would be more context or location modulated whereas cells within the LEC would be object, or object-in-context modulated. To further characterize the spatial selectivity of cells, units were also recorded while rats foraged in an open field. Cells were found within the LEC that responded selectively to context entry. Some cells in the LEC showed object preference, but the pattern was unstable across 90 trials. These results are anomalous, as other studies found cells with the LEC that selected objects in comparable object discrimination tasks. We found cells within the MEC that selected right vs. left context entry, that showed spatial selectivity, and that showed object selectivity. These results indicate that both the MEC and LEC show task-relevant firing, but that the MEC may have a larger role in object-context associations.

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Onusic, Gustavo Massaro. "Distribuição da proteína Fos no lobo temporal medial de ratos Wistar durante o medo condicionado ao contexto, luz e som." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-25022011-183733/.

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No condicionamento clássico de medo, os animais são treinados associando-se um estímulo neutro, por exemplo, som, contexto ou luz a um estímulo aversivo incondicionado, como um choque elétrico nas patas. Apos repetidos pareamentos, a presença do estímulo que inicialmente era neutro passa a eliciar uma resposta condicionada de medo no animal. O congelamento é a resposta mais proeminente dos animais expostos aos estímulos condicionados previamente pareados com choques nas patas, sendo freqüentemente utilizado como medida de medo condicionado (MC). Circuitos cerebrais independentes subjacentes a diferentes formas de memória, e, dentro de um determinado domínio de memória, o envolvimento de estruturas específicas pode depender do tipo de condicionamento se utilizando contexto ou explícito tais sinais leves ou som. Diversos relatos clínicos têm implicado o prejuízo do lobo temporal medial (LTM) com amnésia retrógrada. Embora muito tenha sido feito para desvendar os circuitos neurais subjacentes ao medo condicionado, utilizando contexto, som ou luz como estímulo condicionado (EC) o envolvimento do LTM nessas formas de condicionamento ainda não está claro. Para abordar esta questão foi avaliada a distribuição de Fos no LTM de ratos após a exposição a um contexto, um som ou luz, previamente emparelhado com choques nas patas. Vinte e quatro horas após as sessões de condicionamento, os animais foram colocados na mesma caixa experimental ou a um contexto distinto ou foram expostos ao som e luz sem receber choques nas patas. Diferença significativa na expressão de Fos foi determinada por análise de regiões do lobo temporal medial (córtex ectorrinal, perirrinal e entorrinal) e do hipocampo ventral. Os resultados comportamentais mostraram que houve congelamento nos três tipos de medo condicionado, mas o padrão de distribuição Fos foi diferente em ratos expostos a estímulos específicos ou contexto previamente emparelhado com choques nas patas. Apesar da saliente aquisição da resposta do medo se simular nas três condições, o achado mais saliente foi uma distribuição selectiva de Fos no córtex ectorrinal, perirrinal e entorrinal do grupo. Surpreendentemente, esses animais não mostraram significativa expressão Fos no hipocampo ventral. Isto sugere que o contexto e estímulos aversivos explícitos apresentam propriedades distintas de mapeamento ao de distribuição de Fos no circuito cortico-hipocampal cerebral. Estes resultados indicam que regiões corticais no LTM parecem ser críticas no armazenamento de informações contextuais, mas não de informações associadas a estímulos explícitos previamente pareados a choques nas patas. Conditioned fear (CF) is one of the most frequently used animal models of associative memory to background or foreground stimuli. Independent brain circuits underlie different forms of memory, and, within a particular memory domain, the involvement of specific structures may depend upon the type of conditioning whether using context or explicit cues such light or tone. Several clinical reports have implicated the damage to the medial temporal lobe (MTL) with retrograde amnesia. Although much has been done to disclose the neural circuits underlying CF using context, tone or light as conditioned stimuli (CS) the involvemet of the MTL in these forms of conditioning is still unclear. To address this issue we assessed the Fos distribution in the MTL of rats following exposure to a context, a tone or a light previously paired with footshocks. Twenty-four hours later the conditioning sessions they were placed to the same chamber or to a distinct context and presented with tone or light only without any footshocks. Significant group differences in regional Fos expression were determined by analysis in regions of the medial temporal lobe (ectorhinal, perirhinal and entorhinal cortices) and the ventral hippocampus. The behavioral results showed comparable freezing in the three types of CF but the pattern of Fos distribution was distinct in rats exposed to specific cues or context previously paired with footshocks. Despite comparable acquisition of the conditioned fear response, the most remarkable finding was a selective distribution of Fos in the entorhinal, perirhinal and ectorhinal cortices of the MTL for context-CS groups. Remarkably, these animals did not show significant Fos expression in the ventral hippocampus. It is suggested that context and explicit stimuli endowed with aversive properties through conditioning cause distinct Fos brain mapping in the corticohippocampal circuitry. These results indicate that tasks requiring the association between context and an aversive stimulus depend on subregions of the MTL. Such findings suggested that cortical regions of the MTL appears to be critical for storing context but not explicit cue footshock associations.

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Arboit, Alberto [Verfasser], and Oliver [Gutachter] Stork. "Involvement of TRPC4 and TRPC5 channels in persistent firing in the hippocampus and in the medial entorhinal cortex / Alberto Arboit ; Gutachter: Oliver Stork." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2021. http://d-nb.info/1239811489/34.

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Jacob, Pierre-Yves. "Rôle du cortex entorhinal médian dans le traitement des informations spatiales : études comportementales et électrophysiologiques." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4702/document.

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Le travail de recherche réalisé au cours de cette thèse s'intéresse à la nature des représentations spatiales formées par le cortex entorhinal médian (CEM). Tout d'abord, nous montrons que le CEM code spécifiquement une information de distance, l'une des composantes nécessaires pour que l'animal puisse réaliser un type de navigation reposant sur les informations idiothétiques, appelé intégration des trajets. Puis, nous observons que le système vestibulaire, une source importante d'informations idiothétiques, influence l'activité thêta du CEM et permet la modulation de ce rythme thêta par la vitesse de déplacement des animaux. Ensuite, nous montrons que l'activité du CEM est nécessaire à la stabilité de l'activité des cellules de lieu. Parallèlement, nous observons que l'activité des cellules grilles du CEM est modifiée par les informations contenues dans l'environnement (allothétiques).Dans leur ensemble, nos résultats montrent que le CEM traite et intègre des informations idiothétiques mais aussi des informations allothétiques. Ces données suggèrent que la carte spatiale du CEM ne fournit pas une métrique universelle reposant sur les informations idiothétiques, mais possède un certain degré de flexibilité en réponse aux changements environnementaux. De plus, cette carte spatiale entorhinale n'est pas requise pour la formation de l'activité spatiale des cellules de lieu, contrairement à ce que suggère l'hypothèse dominante The work conducted during my PhD thesis was aimed at understanding the nature of the spatial representation formed by the the medial entorhinal cortex (MEC). First, we show that the MEC codes specifically distance information which is necessary for a type of navigation based on idiothetic cues, called path integration. Then, we observe that the vestibular system, an important source of idiothetic information in the brain, influences the MEC theta rhythm and its modulation by the animal velocity. In addition, we show that MEC activity is necessary for the stability of place cells activity. Finally, we observe that entorhinal grid cells activity is modified by the information available in the environment (allothetic information).Together, our results show that the MEC processes and integrates idiothetic information as well as allothetic information. These data suggest that the entorhinal map is not a universal metric based on idiothetic information, but is flexible and dependant on the information present in the environment. In addition, the entorhinal map is not required for the generation of place cells activity, contrary to the dominant hypothesis

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Allison, Elizabeth Anastasia Margaret Alice. "Exploring the roles of inputs to hippocampal area CA1." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23453.

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Place cells in the hippocampus fire in specific locations within an environment. The aim of this thesis is to investigate the different inputs to the hippocampus and what they contribute to place cell activity and performance of hippocampus-dependent tasks. Place cell activity can also be modulated by relevant features of a task such as a future destination or trajectory. Initial experiments investigated the origin and function of this trajectory-dependent activity and later experiments targeted the medial entorhinal cortex inputs to the hippocampal formation and investigated what they contributed to place cell activity and behaviour. The purpose of the first study was to determine whether trajectory dependent activity occurs in CA3 in a hippocampus-dependent serial-reversal task on the double-Y-maze and to compare it with that seen in CA1. Place cells in both CA3 and CA1 were recorded in rats trained on a serial-reversal task on a double-Y-maze. Rats were trained to run from a start box through two Y-junctions to one of four goal locations. After 10 trials the reward was moved to a new location, until all the boxes had been rewarded. Previous research has found that 44% of CA1 place cells with fields in the start areas of the maze show trajectory-dependent activity in rats trained on the task. This study found that a similar proportion of CA3 place cells also show trajectory-dependent activity in rats trained on this task and that this activity develops at the same time point as the task is learned. This result suggests that trajectory-dependent activity may be generated earlier in the circuit than CA1. Secondly, the contribution of the nucleus reuniens (N.Re) to spatial tasks was investigated. Previously, trajectory-dependent activity has been found to reach the hippocampus via N.Re, however this was shown in a hippocampus-independent task. To investigate the possible role that this input may play in behaviour, N.Re was lesioned and animals were tested on acquisition and performance of the double-Y-maze serial-reversal task described previously. Surprisingly, lesions had no effects on either learning or performance. Taken together with previous data from other studies, this suggests that trajectory dependent activity is not one unique phenomenon but is rather multiple similar phenomena which may originate in different brain regions and fulfil different roles in navigation depending on the demands of the task. In addition, animals were tested on tasks involving allocentric or egocentric navigation. Results suggest that N.Re may have a role in the selection or performance of allocentric navigation but not egocentric navigation. Thirdly, the role of inputs from the medial entorhinal cortex (MEC) to place cells was investigated. Consistent with previous research, MEC lesions resulted in larger, less precise place fields in CA1 place cells. By performing cue-rotation experiments using either distal or proximal cues it was observed that place fields in the MEC lesion animals were not anchored to distal cues but were either stable or anchored to other aspects of the environment. However, place cells in the MEC lesion group still followed proximal cues suggesting that the deficit is restricted to distal landmarks. This suggests that the MEC may process distal landmark information allowing the use of distal landmarks for orientation and self-location within an environment. This thesis contributes a better understanding of the role and origins of trajectory dependent activity as well as a novel finding that the MEC contributes information about distal landmarks to the hippocampus.

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Henley, Benjamin. "Characterising the anti-convulsant effects of CBD and CBDV on layer II of the medial entorhinal cortex of rat and human brain tissue in vitro." Thesis, Aston University, 2018. http://publications.aston.ac.uk/37675/.

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Epilepsy is a common and serious neurological disorder, which manifests in seizures, and has an incidence of approximately 1% of the world population. In developed nations, most instances are relatively well controlled through the use of anti-epileptic drugs (AEDs). For around a third of cases, AEDs are ineffective, resulting in poorly maintained seizures otherwise known as refractory, or drug-resistant epilepsy (DRE). Currently, treatment of DRE often requires neurosurgery to be performed to resect seizure generating foci. Historically, such treatment was used as a last resort due to the invasive and higher risk nature of neurosurgery. More recently, however, surgical intervention has been performed much earlier in order to achieve better long-term patient outcomes. Notwithstanding this, DRE presents a major and as of yet, unmet clinical need for new and effective antiepileptic drugs to be found. In vitro and in vivo electrophysiological methods have been used investigate epilepsy for many years. Neuronal network oscillations and single cell patching recordings between physiological and pathophysiological samples provide a basis to compare alterations between normal and epileptic brain tissue. In terms of electrophysiological approaches, the hippocampus and entorhinal cortex (EC) are two of the most commonly studied areas of the brain, especially in relation to temporal lobe epilepsy (TLE). Plant derived cannabinoids – phytocannabinoids – have been proposed as effective AEDs for DRE cases. In particular the non-psychoactive phytocannabinoids cannabidiol (CBD) and cannabidivarin (CBDV), with recent clinical trials supporting this claim. The present study is an investigation into whether CBD and CBDV are suitable and effective AEDs, and to identify their mechanism(s) of action. Electrophysiological recordings of medial entorhinal cortex (mEC) layer II principal cells have been studied due to their relative importance and participation in TLE. Alterations in oscillatory rhythms and single cell responses were compared between RISE afflicted epileptic rats (SE rats) and wild type, age matched controls (AMC). Experiments on human tissue resected from children with TLE were also performed, concurrent with the rodent experiments. Key findings from this project show CBD(V) suppressant effects on induced gamma oscillations, in an age- and disease-dependent manner in rat tissue, suggesting damping of neuronal network excitability. Further to this, CBD induces increased GABA inhibition onto rat medial entorhinal principal cells as evidenced by increases in mean median decay times and inhibitory charge transfer across the postsynaptic membrane, while CBDV did not show this effect. The effects of CBD were effectively blocked by both GABAAR and NMDAR antagonists, suggesting interaction with both of these receptors to exert the response. CBD also showed additive effect to low-dose benzodiazepine and barbiturate agonists and a ceiling effect at higher doses, suggestive of an allosteric action on the GABAAR. Similar effects were also noted in the human tissue cells, suggestive of an analogous mechanism of action in humans. Hence, we postulate that CBD is acting at both postsynaptic GABAARs, as a positive allosteric modulator (PAM) and, at pre-/postsynaptic NMDARs, either directly or indirectly, to positively influence GABA signalling mechanisms causing an increase in inhibitory activity at postsynaptic principal cells resulting in decreased neuronal excitability.

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Huff, Mary Louise. "Separate basolateral amygdala projections to the hippocampal formation differentially modulate the consolidation of contextual and emotional learning." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2223.

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Previous research investigating the neural circuitry underlying memory consolidation has primarily focused on single “nodes” in the circuit rather than the neural connections between brain regions, despite the likely importance of these connections in mediating different aspects or forms of memory. This focus has, in part, been due to technical limitations; however the advent of optogenetics has altered our capabilities in this regard, enabling optical control over neural pathways with temporal and spatial precision. The current set of experiments took advantage of optogenetics to control activity in specific pathways connecting brain regions in rats immediately after different kinds of learning. Chapter 2 first established the use of optogenetics to manipulate activity in the basolateral amygdala (BLA), which has been shown to modulate memory consolidation for a variety of types of learning likely through its connections to various downstream regions. Using a one-trial inhibitory avoidance task, a simple and robust fear learning paradigm, we found that both post-training stimulation and inhibition of BLA activity could enhance or impair later retention of the task, respectively. Enhancement was specific to stimulation using trains of 40, but not 20, Hz light pulses. Chapters 3 and 4 examined the projections from the BLA to the ventral hippocampus (VH) and medial entorhinal cortex (mEC) as the BLA’s ability to influence the consolidation for many types of memory is believed to be mediated through discrete projections to distinct brain regions. Indeed, the BLA innervates both structures, and prior studies suggest that the mEC and VH have distinct roles in memory processing related to contextual and nociceptive (footshock) learning, such as those involved in contextual fear conditioning (CFC). Optogenetic stimulation or inhibition of the BLA-VH or BLA-mEC pathway after training on a modified CFC task, in which the nociceptive or emotional stimulus (the footshock) and the context are separated, enabled experimental manipulations to selectively affect the consolidation for learning about one component and not the other. Optogenetic stimulation/inhibition was given to each candidate pathway immediately after the relevant training to determine its role in influencing consolidation for that component of the CFC learning. Chapter 3 results showed that stimulation of the BLA-VH pathway following footshock, but not context, training enhanced retention, an effect that was specific to trains of 40 Hz stimulation. Post-footshock photoinhibition of the same pathway impaired retention for the task. Similar investigations of the BLA-mEC pathway in Chapter 4 produced complementary findings. Post-context, but not footshock, stimulation of the pathway enhanced retention. In this particular case, only trains of 8 Hz stimulation were effective at enhancing retention. These results are the first, to our knowledge, to find that BLA inputs to different structures selectively modulate consolidation for different aspects of learning, thus enhancing our understanding of the neural connections underlying the consolidation of contextual fear conditioning and providing a critical foundation for future research.

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Persson, Bjorn Martin. "Cognitive and neural processes underlying memory for time and context." Thesis, University of St Andrews, 2017. http://hdl.handle.net/10023/11024.

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The aim of this thesis is to examine the underlying cognitive and neural processes at play during retrieval of temporal and contextual source information. This was assessed across three experimental chapters. In the first experimental chapter, Chapter 2, the neural loci of context associations were assessed. Rats trained on an odour-context association task were given lesions to either the Lateral Entorhinal Cortex (LEC) or sham lesions. After surgery, performance on the odour-context task was assessed. It was hypothesised that memory for previously learned odour-context associations would be impaired following LEC lesions but not sham lesions. The results supported this hypothesis, demonstrating impaired memory for the previously learned odour-context associations in the LEC lesion group compared to the Sham lesion. In Chapter 3, the underlying retrieval processes used to retrieve time and context in human memory was assessed across three experiments. It was hypothesised that time would be remembered accurately using both recollection and familiarity, while correct context memory should rely on recollection alone. Two out of the three experiments supported this hypothesis, demonstrating that temporal information can be retrieved using familiarity in certain instances. The final experimental Chapter 4 used fMRI to extend Chapter 3 and examine whether neural activity would be greater in regions associated with recollection during memory for context, while activity in familiarity-related regions would be higher during memory for time. Results revealed no support for these predictions with no regions linked to recollection showing greater context-related activity, and no regions previously linked to familiarity exhibiting increased activation as temporal information was retrieved. The results are discussed in relation to established recollection and familiarity frameworks and previous work examining the neural substrates supporting memory for time and context.

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Didic-Hamel, Cooke Mira. "Apport de l'étude des systèmes mnésiques mesiotemporaux au diagnostic précoce de la Maladie d'Alzheimer débutante." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20651.

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Un nombre croissant de travaux chez l’animal et chez l’homme suggèrent que les différentes structures composant le lobe temporal interne (LTI) contribuent de manière différentielle à la mémoire déclarative. Chez l’homme, deux réseaux neuraux impliquant le LTI sont décrits : un réseau mésiotemporal antérieur, constitué de structures pour lesquelles les études chez les patients cérébro-lésés indiquent qu’elles contribueraient à la mémoire décontextualisée (mémoire des objets et mémoire sémantique ou mémoire du « quoi ») ; un réseau mésiotemporal postérieur, constitué d’autres structures pour lesquelles ces études suggèrent plutôt une implication dans la mémoire contextualisée (mémoire spatiale, épisodique ou mémoire du «où » et du « quand»). Dans la Maladie d’Alzheimer (MA), les dégénérescences neurofibrillaires, dont la distribution topographique est corrélée à la nature des déficits cognitifs, se développent initialement dans les cortex sous-hippocampiques - transentorhinal et entorhinal - qui sont des composants du réseau mésiotemporal antérieur, avant de s’étendre à l’hippocampe. Les éventuels déficits cognitifs en relation avec l’atteinte de cette région ne sont pas clairement identifiés dans la MA. Les travaux présentés dans ce mémoire sont centrés sur l’étude des cortex sous-hippocampiques avec les méthodes de la neuropsychologie et la neuroimagerie. Ils suggèrent que la MA aux stades les plus précoces pourrait représenter un « modèle » d’étude privilégié des systèmes mnésiques auxquels contribue le LTI. Ces résultats sont en faveur de l’utilité de l’évaluation de la mémoire décontextualisée dans le diagnostic de la MA débutante There is increasing evidence from experiments in rodents and non-human primates, as well as from human studies, to suggest that the different structures within the medial temporal lobe (MTL) differentially contribute to declarative memory. In the human brain, two neural networks implicating MTL structures have been described: an anterior MTL network that includes brain areas that contribute to context-free memory (object memory and semantic memory or memory for « what ») and a posterior MTL network that contributes to context-rich memory (spatial memory, episodic memory or memory for “where” and “when”). In Alzheimer’s disease (AD), neurofibrillary tangles (NFT), associated with cognitive signs, initially appear in the sub-hippocampal (transentorhinal and entorhinal) cortex, which are part of the anterior MTL network, before reaching the hippocampus. Potential cognitive deficits related to the dysfunction of this brain area in AD are not clearly identified. In the presented studies, the emphasis is placed on the investigation of sub-hippocampal corteces using a neuropsychological approach and neuroimaging techniques. Our findings suggest that the very earliest stages of AD could represent a “model” leading to a better understanding of memory systems that involve the MTL. They also provide evidence that evaluating context-free memory may be useful in the diagnosis of early AD

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DiMauro, Audrey. "Functional interactions between the hippocampus, medial entorhinal cortex and medial prefrontal cortex for spatial and nonspatial processing." Thesis, 2014. https://hdl.handle.net/2144/15401.

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Memory formation and recall depend on a complex circuit that includes the hippocampus and associated cortical regions. The goal of this thesis was to understand how two of the cortical connections, the medial entorhinal cortex (MEC) and medial prefrontal cortex (mPFC), influence spatial and nonspatial activity in the hippocampus. Cells in the MEC exhibit prominent spatially selective activity and have been hypothesized to drive place representation in the hippocampus. In Experiment 1 the MEC was transiently inactivated using the inhibitory opsin ArchaerhodopsinT (ArchT), and simultaneous recordings from CA1 were made as rats ran on an elliptical track. In response to MEC disruption some cells in the hippocampus shifted the preferred location of activity, some changed firing rate and others were unaffected. The new representation that developed following MEC disruption remained stable despite the fact that inhibition was transient. If the MEC is the source of spatial activity in the hippocampus the activity would be either time-locked to periods of inhibition or unstable throughout the period of inconsistent input. These results show that the MEC guides spatial representation in the hippocampus but does not directly drive spatial firing. The mPFC is generally thought to guide behavior in response to contextual elements. Experiment 2 examined the interaction between the mPFC and the hippocampus as rats performed a contextual discrimination task. Recordings were made in CA1, and the mPFC was disrupted using ArchT during the odor sampling phase of the discrimination. As animals perform this task neurons in the hippocampus respond to a conjunction of odor and location which indicates an association of what and where information in the hippocampus. Optogenetic disruption of the mPFC led to a decrease in nonspatial representation. Individual cells showed lower levels of odor selectivity, but there was no change in the level of spatial representation. This indicates that the mPFC is important for determining how the hippocampus represents nonspatial information but does not alter the spatial representation. The results are discussed within a model of memory formation that includes binding spatial and nonspatial information in the hippocampus.

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Monaghan, Caitlin. "Effects of pharmacological manipulations on activity in the medial entorhinal cortex." Thesis, 2016. https://hdl.handle.net/2144/16727.

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Animal research involving the effects of anxiolytics on theta oscillations has focused on changes in theta frequency in the hippocampus, rather than effects in medial entorhinal cortex (MEC), which provides the cortical input to the hippocampus and is the source of Type I (movement-related) theta rhythm. Neurons coding spatial location, including “grid cells,” are found in the MEC and aspects of their spatial modulation have been linked to theta rhythm in different ways. Theta frequency recorded in the local field potential (LFP) is also strongly correlated with running speed and is used in specific computational models of grid cell firing. Manipulating theta frequency through administration of anxiolytics offers a unique method of examining regulation of the LFP frequency in the MEC, along with the effects of changes in theta frequency on grid cells and other cell types in the region. In addition, the role of the medial septum (MS), which is necessary for theta rhythm in both the MEC and hippocampus, can be investigated by infusing anxiolytics directly into the MS. In this thesis, two separate anxiolytic drugs were tested: a serotonin 1A receptor agonist, 8-OH-DPAT, and a classic benzodiazepine, diazepam, the results of which are described in chapters 2 and 3, respectively. Systemic injections of either drug caused a reduction in theta frequency across all running speeds, resulting in a decrease in the y-intercept of the linear fit to the plot of theta frequency over different running speeds. However, only MS infusion of 8-OH-DPAT, not diazepam, significantly decreased the y-intercept in the MEC. Together, these results expand detection of anxiolytic drug action on theta frequency to a new structure, the MEC, when drugs are given systemically, but demonstrate a dissociation between drug types in their ability to produce effects when infused into the MS. Grid cell firing patterns were unaffected and very few effects were found in single unit firing across different cell types. Overall, these results support predictions made by specific computational models and highlight the involvement of the MEC in the anxiolytic-induced decrease in theta frequency phenomenon uniquely tied to the action of these drugs.

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"Modulation of medial entorhinal cortex layer II cell circuitry by stress hormones." Tulane University, 2017.

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Shay, Christopher Frank. "Cellular properties of the medial entorhinal cortex as possible mechanisms of spatial processing." Thesis, 2015. https://hdl.handle.net/2144/16251.

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Cells of the rodent medial entorhinal cortex (EC) possess cellular properties hypothesized to underlie the spatially periodic firing behaviors of 'grid cells' (GC) observed in vivo. Computational models have simulated experimental GC data, but a consensus as to what mechanism(s) generate GC properties has not been reached. Using whole cell patch-clamp and computational modeling techniques this thesis investigates resonance, rebound spiking and persistent spiking properties of medial EC cells to test potential mechanisms generating GC firing. The first experiment tested the voltage dependence of resonance frequency in layer II medial EC stellate cells. Some GC models use interference between velocity-controlled oscillators to generate GCs. These interference mechanisms work best with a linear relationship between voltage and resonance frequency. Experimental results showed resonance frequency decreased linearly with membrane potential depolarization, suggesting resonance properties could support the generation of GCs. Resonance appeared in medial EC but not lateral EC consistent with location of GCs. The second experiment tested predictions of a recent network model that generates GCs using medial EC stellate cell resonance and rebound spiking properties. Sinusoidal oscillations superimposed with hyperpolarizing currents were delivered to layer II stellate cells. Results showed that relative to the sinusoid, a limited phase range of hyperpolarizing inputs elicited rebound spikes, and the phase range of rebound spikes was even narrower. Tuning model parameters of the stellate cell population to match experimental rebound spiking properties resulted in GC spatial periodicity, suggesting resonance and rebound spiking are viable mechanisms for GC generation. The third experiment tested whether short duration current inputs can induce persistent firing and afterdepolarization in layer V pyramidal cells. During muscarinic acetylcholine receptor activation 1-2 second long current injections have been shown to induce persistent firing in EC principal cells. Persistent firing may underlie working memory performance and has been used to model GCs. However, input stimuli during working memory and navigation may be much shorter than 1-2 seconds. Data showed that input durations of 10, 50 and 100 ms could elicit persistent firing, and revealed time courses and amplitude of afterdepolarization that could contribute to GC firing or maintenance of working memory.

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Morrissey, Mark. "Separating the Functions of the Medial and Lateral Entorhinal Cortex: Differential Involvement in Spatial and Non-spatial Memory Retrieval." Thesis, 2011. http://hdl.handle.net/1807/31349.

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Anatomical connectivity and single neuron coding suggest a dissociation of information representation within the lateral and medial entorhinal cortex, a brain region with widespread connections to cortical areas. We aimed to expand this idea by examining differential contribution of these two sub-regions to the retrieval of non-spatial and spatial memory. Inactivation of lateral, but not medial regions severely impaired the retrieval of recently and remotely acquired non-spatial memory while spatial memory remained intact. To link functioning of the lateral entorhinal cortex with the known roles of the hippocampus and medial prefrontal cortex for memory retrieval, communication with these two regions was detected as synchronized oscillations in local field potentials. We found that stronger communication between the lateral entorhinal and prefrontal cortex during stimulus-free periods correlated with better memory performance. The lateral entorhinal cortex therefore may serve as a gateway of memory-related information between the medial prefrontal and other cortical regions.

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Newmark, Randall. "High resolution fMRI of hippocampal subfields and medial temporal cortex during working memory." Thesis, 2014. https://hdl.handle.net/2144/14297.

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Computational models combined with electrophysiological studies have informed our understanding about the role of hippocampal subfields (dentate gyrus, DG; CA subfields, subiculum) and Medial Temporal Lobe (MTL) cortex (entorhinal, perirhinal, parahippocampal cortices) during working memory (WM) tasks. Only recently have functional neuroimaging studies begun to examine under which conditions the MTL are recruited for WM processing in humans, but subfield contributions have not been examined in the WM context. High-resolution fMRI is well suited to test hypotheses regarding the recruitment of MTL subregions and hippocampal subfields. This dissertation describes three experiments using high-resolution fMRI to examine the role of hippocampal subfields and MTL structures in humans during WM. Experiment 1 investigated MTL activity when participants performed a task that required encoding and maintaining overlapping and non-overlapping stimulus pairs during WM. During encoding, activity in CA3/DG and CA1 was greater for stimulus pairs with overlapping features. During delay, activity in CA1 and entorhinal cortex was greater for overlapping stimuli. These results indicate that CA3/DG and CA1 support disambiguating overlapping representations while CA1 and entorhinal cortex maintain these overlapping items. Experiment 2 investigated MTL activity when participants performed a WM task that required encoding and maintaining either low or high WM loads. The results show a load effect in entorhinal and perirhinal cortex during the delay period and suggest that these regions act as a buffer for WM by actively maintaining novel information in a capacity-dependent manner. Experiment 3 investigated MTL activity when participants performed a WM task that required maintaining similar and dissimilar items at different loads. Analysis of a load by similarity interaction effect revealed areas of activity localized to the CA1 subfield. CA1 showed greater activity for higher WM loads for dissimilar, but not similar stimuli. Our findings help identify hippocampal and MTL regions that contribute to disambiguation in a WM context and regions that are active in a capacity-dependent manner which may support long-term memory formation. These results help inform our understanding of the contributions of hippocampal subfields and MTL subregions during WM and help translate findings from animal work to the cognitive domain of WM in humans.

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Tanninen, Stephanie. "Direct Connections between the Lateral Entorhinal Cortex and Hippocampus or Medial Prefrontal cortex: Their Role in the Retrieval of Associative Memories." Thesis, 2012. http://hdl.handle.net/1807/33556.

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Consolidation of associative memories may depend on communication between the lateral entorhinal cortex (LEC) and hippocampus (HPC) for recently learned memories and the LEC and medial prefrontal cortex (mPFC) for remote memories. To determine whether direct connections between these regions are necessary for the retrieval of a recently or remotely learned memory, rats acquired an associative memory through trace eyeblink conditioning and were tested for memory retention after inactivating the regions of interest with the GABAA agonist, muscimol. Inactivating the LEC-HPC connection did not impair memory retrieval. However, inactivating the LEC-mPFC connection impaired remote, but not recent, memory retrieval. Thus, the LEC and mPFC connection is necessary for the retrieval of a remotely, but not recently learned associative memory. Increased reliance on the entorhinal-prefrontal connection indicates the strengthening of functional connectivity between the two regions, which may be a biological correlate for the proposed reorganization during systems consolidation.

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Robinson, Nicholas Timothy Mark. "The role of medial entorhinal cortex activity in hippocampal CA1 spatiotemporally correlated sequence generation and object selectivity for memory function." Thesis, 2016. https://hdl.handle.net/2144/16728.

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The hippocampus is crucial for episodic memory and certain forms of spatial navigation. Firing activity of hippocampal principal neurons contains environmental information, including the presence of specific objects, as well as the animal’s spatial and temporal position relative to environmental and behavioral cues. The organization of these firing correlates may allow the formation of memory traces through the integration of object and event information onto a spatiotemporal framework of cell assemblies. Characterizing how external inputs guide internal dynamics in the hippocampus to enable this process across different experiences is crucial to understanding hippocampal function. A body of literature implicates the medial entorhinal cortex (MEC) in supplying spatial and temporal information to the hippocampus. Here we develop a protocol utilizing bilaterally implanted custom designed triple fiber optic arrays and the red-shifted inhibitory opsin JAWS to transiently inactivate large volumes of MEC in freely behaving rats. This was coupled with extracellular tetrode recording of ensembles in CA1 of the hippocampus during a novel memory task involving temporal, spatial and object related epochs, in order to assess the importance of MEC activity for hippocampal feature selectivity during a rich and familiar experience. We report that inactivation of MEC during a mnemonic temporal delay disrupts the existing temporal firing field sequence in CA1 both during and following the inactivation period. Neurons with firing fields prior to the inactivation on each trial remained relatively stable. The disruption of CA1 temporal firing field sequences was accompanied by a behavioral deficit implicating MEC activity and hippocampal temporal field sequences in effective memory across time. Inactivating MEC during the object or spatial epochs of the task did not significantly alter CA1 object selective or spatial firing fields and behavioral performance remained stable. Our findings suggest that MEC is crucial specifically for temporal field organization and expression during a familiar and rich experience. These results support a role for MEC in guiding hippocampal cell assembly sequences in the absence of salient changing stimuli, which may extend to the navigation of cognitive organization in humans and support memory formation and retrieval.

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Dissertations / Theses on the topic 'Medial Entorhinal Cortex (MEC)'

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