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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Cracking the brain's code : how do brain rhythms support information processing?

Constantinou, Maria January 2017 (has links)
The brain processes information sensed from the environment and guides behaviour. A fundamental component in this process is the storage and retrieval of past experiences as memories, which relies on the hippocampal formation. Although there has been a great progress in understanding the underlying neural code by which neurons communicate information, there are still open questions. Neural activity can be measured extracellularly as either spikes or field potentials. Isolated spikes and bursts of high-frequency spikes followed by silent periods can transmit messages to distant networks. The local field potential (LFP) reflects synaptic activity within a local network. The interplay between the two has been linked to cognitive functions, such as memory, attention and decision making. However, the code by which this neural communication is achieved is not well understood. We investigated a mechanism by which local network information contained in LFP rhythms can be transmitted to distant networks in the formof spike patterns fired by bursting neurons. Since rhythms within different frequency bands are prevalent during behavioural states, we studied this encoding during different states within the hippocampal formation. In the first paper, using a computational model we show that bursts of different size preferentially lock to the phase of the dominant rhythm within the LFP.We also present examples showing that bursting activity in the subiculum of an anaesthetised rat was phase-locked to delta or theta rhythms as predicted by the model. In the second paper, we explored possible neural codes by which bursting neurons can encode features of the LFP.We used the computational model reported in the first paper and analysed recordings from the subiculum of anaesthetised rats and the medial entorhinal cortex of an awake behaving rat. We show that bursting neurons encoded information about the instantaneous voltage, phase, slope and/or amplitude of the dominant LFP rhythm (delta or theta) in their firing rate. In addition, some neurons encoded about 10-15% of this information in intra-burst spike counts. We subsequently studied how the interactions between delta or theta rhythms can transfer information between different areas within the hippocampal formation. In the third paper, we show that delta and theta rhythms can act as separate routes for simultaneously transferring segregate information between the hippocampus and the subiculum of anaesthetised mice. We found that the phase of the rhythms conveyed more information than amplitude. We next investigated whether neurodegenerative pathology affects this information exchange. We compared information transfer within the hippocampal formation of young transgenic mice exhibiting Alzheimer’s disease-like pathology and healthy aged-matched control mice and show that at early stages of the disease the information transmission by LFP rhythm interactions appears to be intact but with some differences. The outcome of this project supports a burst code for relaying information about local network activity to downstream neurons and underscores the importance of LFP phase, which provides a reference time frame for coordinating neural activity, in information exchange between neural networks.
52

Beyond AMPA and NMDA: Slow synaptic mGlu/TRPC currents : Implications for dendritic integration

Petersson, Marcus January 2010 (has links)
<p>In order to understand how the brain functions, under normal as well as pathological conditions, it is important to study the mechanisms underlying information integration. Depending on the nature of an input arriving at a synapse, different strategies may be used by the neuron to integrate and respond to the input. Naturally, if a short train of high-frequency synaptic input arrives, it may be beneficial for the neuron to be equipped with a fast mechanism that is highly sensitive to inputs on a short time scale. If, on the contrary, inputs arriving with low frequency are to be processed, it may be necessary for the neuron to possess slow mechanisms of integration. For example, in certain working memory tasks (e. g. delay-match-to-sample), sensory inputs may arrive separated by silent intervals in the range of seconds, and the subject should respond if the current input is identical to the preceeding input. It has been suggested that single neurons, due to intrinsic mechanisms outlasting the duration of input, may be able to perform such calculations. In this work, I have studied a mechanism thought to be particularly important in supporting the integration of low-frequency synaptic inputs. It is mediated by a cascade of events that starts with activation of group I metabotropic glutamate receptors (mGlu1/5), and ends with a membrane depolarization caused by a current that is mediated by canonical transient receptor potential (TRPC) ion channels. This current, denoted I<sub>TRPC</sub>, is the focus of this thesis.</p><p>A specific objective of this thesis is to study the role of I<sub>TRPC</sub> in the integration of synaptic inputs arriving at a low frequency, < 10 Hz. Our hypothesis is that, in contrast to the well-studied, rapidly decaying AMPA and NMDA currents, I<sub>TRPC</sub> is well-suited for supporting temporal summation of such synaptic input. The reason for choosing this range of frequencies is that neurons often communicate with signals (spikes) around 8 Hz, as shown by single-unit recordings in behaving animals. This is true for several regions of the brain, including the entorhinal cortex (EC) which is known to play a key role in producing working memory function and enabling long-term memory formation in the hippocampus.</p><p>Although there is strong evidence suggesting that I<sub>TRPC</sub> is important for neuronal communication, I have not encountered a systematic study of how this current contributes to synaptic integration. Since it is difficult to directly measure the electrical activity in dendritic branches using experimental techniques, I use computational modeling for this purpose. I implemented the components necessary for studying I<sub>TRPC</sub>, including a detailed model of extrasynaptic glutamate concentration, mGlu1/5 dynamics and the TRPC channel itself. I tuned the model to replicate electrophysiological in vitro data from pyramidal neurons of the rodent EC, provided by our experimental collaborator. Since we were interested in the role of I<sub>TRPC</sub> in temporal summation, a specific aim was to study how its decay time constant (τ<sub>decay</sub>) is affected by synaptic stimulus parameters.</p><p>The hypothesis described above is supported by our simulation results, as we show that synaptic inputs arriving at frequencies as low as 3 - 4 Hz can be effectively summed. We also show that τ<sub>decay</sub> increases with increasing stimulus duration and frequency, and that it is linearly dependent on the maximal glutamate concentration. Under some circumstances it was problematic to directly measure τ<sub>decay</sub>, and we then used a pair-pulse paradigm to get an indirect estimate of τ<sub>decay</sub>.</p><p>I am not aware of any computational model work taking into account the synaptically evoked I<sub>TRPC</sub> current, prior to the current study, and believe that it is the first of its kind. We suggest that I<sub>TRPC</sub> is important for slow synaptic integration, not only in the EC, but in several cortical and subcortical regions that contain mGlu1/5 and TRPC subunits, such as the prefrontal cortex. I will argue that this is further supported by studies using pharmacological blockers as well as studies on genetically modified animals.</p> / QC 20101005
53

Distribuição da proteína Fos no lobo temporal medial de ratos Wistar durante o medo condicionado ao contexto, luz e som / Fos distribution in the medial temporal lobe during context-, auditory- and light-cued conditioned fear in Wistar rats.

Onusic, Gustavo Massaro 26 November 2010 (has links)
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.
54

Large-scale circuit reconstruction in medial entorhinal cortex

Schmidt-Helmstaedter, Helene 28 May 2018 (has links)
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.
55

Principles of local computation in the entorhinal cortex

Reifenstein, Eric 21 October 2016 (has links)
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.
56

Die funktionelle Bedeutung von Projektionszellen des medialen entorhinalen Cortex in der Interaktion zwischen entorhinalem Cortex und Hippocampus

Gloveli, Tengis 14 November 2000 (has links)
Der entorhinale Cortex (EC) nimmt eine zentrale Stellung im limbischem System ein und ist darüber hinaus eine Verbindungsstelle zwischen Hippocampus und Cortex. Um die Eigenschaften der Projektionszellen im EC genauer zu charakterisieren, führten wir intrazelluläre Ableitungen an den Neuronen der oberflächlichen (Schicht II und III) und der tiefen (Schicht IV-VI) Schichten durch, von denen etwa ein Viertel während der Ableitung mit dem Farbstoff Biozytin gefärbt werden konnten. In Schicht III des medialen EC fanden wir vier unterschiedliche Zelltypen, von denen zwei als Projektionsneurone (Typ 1 und Typ 2) charakterisiert wurden. Die Projektionszellen der Schicht III besitzen eine niedrige Schwelle zur Auslösung synaptisch evozierter Aktionspotentiale. Daneben konnten wir zwei weitere Typen von Zellen (Typ 3 und Typ 4) bestimmen, deren Somata in der Schicht III lagen, die aber nicht in den Hippocampus projizierten, sondern lokal im EC verschaltet waren. In den tiefen Schichten des EC fanden sich zur Area Dentata (AD) projezierende bipolare und multipolare Neurone, die trotz der morphologischen Ähnlichkeit mit GABAergen Interneuronen die typischen elektrophysiologischen und neurochemischen Eigenschaften von Prinzipalzellen des EC besitzen. Diese Neurone können vermutlich Funktionen von sowohl Lokal- als auch Projektionszellen übernehmen und dementsprechend die schnelle Informationsübertragung zwischen den tiefen und oberflächlichen Schichten einerseits und zwischen EC und AD andererseits ausüben. Um der Frage nachzugehen, unter welchen Bedingungen die Schicht II- und III-Projektionszellen aktiviert werden, führten wir repetitive synaptische Reizungen im EC durch. Hochfrequente repetitive synaptische Reizung (> 10 Hz) führt zu einer bevorzugten Aktivierung der Schicht II-Zellen. Hingegen werden die Schicht III-Zellen bei niedrigeren Reizfrequenzen (< 6 Hz) bevorzugt aktiviert und Schicht II-Zellen gleichzeitig gehemmt. Dies läßt vermuten, daß der Informationstransfer zwischen EC und Hippocampus frequenzabhängig gesteuert wird. / The entorhinal cortex (EC) occupies a key position in the limbic system because it functions as a relay station between the hippocampus and cortex. To analyze the properties of the projection cells of the EC we used intracellular recordings from superficial (layers II and III) and deep layers (layers IV-VI). Intracellular electrodes contained the marker biocytin and the labeled neurons were processed for posthoc anatomical identification. We can classify medial EC layer III cells into four different types. Type 1 and 2 cells were projection cells. These cells exhibited a low threshold of action potential generation upon synaptic stimulation. We identified the two other, presumed local circuit type 3 and type 4 cells, whose axons remained within the EC. In deep EC layers we described bipolar and multipolar neurons which form projections from the deep layers of the EC to the dentate gyrus (DG). Despite the morphological similarity of these cells to those of GABAergic interneurons in the EC, their electrophysiological characteristics were similar to those of principal neurons. We conclude that neurons of the deep layers of the EC that project to the DG may function both as local circuit and projection neurons thereby providing a rapid transfer of information from deep layers of the EC to the DG and superficial layers of the EC. We next studied how the separate pathways from layers II and III of the EC to the hippocampus are preferentially effective as a function of stimulation frequency. High frequency (>10 Hz) synaptic activation of the EC was more effective at eliciting action potentials from layer II EC neurons. In contrast, during low frequency (
57

Structure function relationships in medial entorhinal cortex

Tang, Qiusong 18 March 2015 (has links)
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.
58

Proliferation von Mikrogliazellen und Astrozyten im Gyrus dentatus der Ratte nach experimenteler Läsion des entorhinalen Kortext

Grampp, Anne 06 October 2000 (has links)
Die Läsion des entorhinalen Kortex bei adulten Ratten induziert in der deafferenzierten Molekularschicht des Gyrus dentatus eine Gliaaktivierung und -proliferation. Histochemische Doppelfärbungen auf das astrozytenspezifische Antigen Glial fibrillary acidic protein oder den Mikrogliamarker Griffonia simplicifolia isolectin B4 und Bromodeoxyuridin haben gezeigt, daß die Mikrogliazellzahlen in der Molekularschicht des Gyrus dentatus 3 Tage nach Läsion (dpl) ein Maximum erreichten und 30 dpl auf Kontrollwerte zurückgingen. Die Astrozytenzahlen im ipsilateralen Gyrus dentatus erreichten 30 dpl ein Maximum, ihre größte Proliferationsaktivität war 7 dpl zu beobachten. 100 dpl waren die Astrozytenzahlen auf Kontrollwerte zurückgegangen. Die Gliaproliferation war nicht auf die ipsilaterale Molekularschicht beschränkt, sondern trat auch zu einem bestimmten Grad in der Körnerzellschicht und im kontralateralen Gyrus dentatus auf. Somit ruft eine entorhinale Kortexläsion eine rasche Mikrogliareaktion und eine langanhaltende Astrozytenaktivierung in der deafferenzierten Terminationszone des Tractus perforans hervor. Schließlich ist zu erwähnen, daß Gliaproliferation nach entorhinaler Läsion einem komplexen zeitlichen und räumlichen Muster folgt, das bei Prozessen der neuronalen und axonalen Reorganisation auftritt. / Entorhinal cortex lesion of adult rats induces glial activation and proliferation in the deafferented dentate molecular layer. Double-labelling immunocytochemistry for the astrocyte-specific antigen glial fibrillary acidic protein or the microglial cell marker Griffonia simplicifolia isolectin B4 with bromodexyuridine detection revealed that microglia counts and the proliferation rate in the ipsilateral dentate gyrus reached a maximum in the molecular layer at 3 days post-lesion (dpl) and returned to control levels by 30 dpl. Astrocyte counts in the ipsilateral dentate gyrus peaked at 30 dpl, with maximum proliferation at 7 dpl. At 100 dpl the astrocyte count had reverted to control levels. Glial proliferation was not restricted to the ipsilateral molecular layer but also occurred to some degree in the granule cell layer and the contralateral dentate gyrus. Thus entorhinal cortex lesion induces a rapid microglial reaction and long-lasting astrocyte activation in the deafferented termination zone of the perforant path. To conclude, glial proliferation after entorhinal cortex lesion follows a complex temporal and spatial pattern that coincides with processes of neuronal and axonal reorganization.
59

Efeito diferencial do diazepam sobre a atividade da enzima Na+,K+-ATPase no hipocampo e córtex entorrinal / Differencial effect of diazepam on Na+,K+-ATPase activity in the hippocampus and entorhinal cortex

Marafiga, Joseane Righes 29 November 2016 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Na+,K+-ATPase is ubiquitously expressed in the plasma membrane of all animal cells where serves as the principal regulator of intracellular ion homeostasis. Na+,K+-ATPase activity is activated by Na+ and K+ and current evidence indicates that total Na+,K+-ATPase activity is, in general, inhibited by anions. However, the effect of pharmacologically-induced Cl- flux on α1- and α2/3-subunit containing Na+,K+-ATPase activity is not established. In this study we investigated the effect of diazepam, a GABAA receptor positive allosteric modulator, on α1- and α2/3-subunit containing Na+,K+-ATPase activity. Hippocampal and cortical slices were incubated with diazepam (0, 0.05, 0.15 or 0.5 μM) and/or flumazenil (0, 0.005, 0.015, 0.05, 0.15, 0.5 or 1.5 μM) for 10 minutes. After incubation the slices were homogenized and α1 and α2/3 Na+,K+-ATPase activity were assayed using ouabain 3 μM (that inhibits α2/3-subunit containing Na+,K+-ATPase) and 4 mM (that inhibits both isoforms). Diazepam caused a 50% decrease of α2/3-subunit containing Na+,K+-ATPase activity in the hippocampus, but did not alter enzyme activity in the entorhinal cortex. The effect of diazepam was prevented by flumazenil, indicating that the decrease of Na+,K+-ATPase was involved GABAA receptors. Furthermore, a low chloride medium abolished the diazepam-induced decrease of Na+,K+-ATPase activity. Our data suggests that Na+,K+-ATPase in the hippocampus is sensitive to the pharmacological effects of a benzodiazepine by GABAA receptor-mediated mechanisms. Keywords: sodium pump. GABAA receptor. diazepam. flumazenil. chloride ion. hippocampus. entorhinal córtex. / A enzima Na+,K+-ATPase, ou bomba de sódio, é expressa na membrana plasmática de células eucarióticas, onde atua como principal regulador da homeostase iônica intracelular. A enzima Na+,K+-ATPase é ativada pelos íons Na+ and K+ e evidências indicam que a atividade total da enzima Na+,K+-ATPase é inibida por ânions. Entretanto, o efeito do fluxo de cloreto induzido farmacologicamente sobre a atividade das subunidades α1 e α2/3 da enzima Na+,K+-ATPase ainda não foi investigado. Neste estudo, nós investigamos o efeito do diazepam, um modulador alostérico positivo do receptor GABAA na atividade específica das subunidades α1 e α2/3 da Na+,K+-ATPase. Fatias de hipocampo e de córtex entorrinal foram incubadas com diazepam (0; 0,05; 0,15 ou 0,5 μM) e/ou flumazenil (0; 0,005, 0,015; 0,05; 0,15; 0,5 ou 1,5 μM) por 10 minutos. Após a incubação, as fatias foram homogeneizadas e a atividade das subunidades α1 e α2/3 da enzima Na+,K+-ATPase foi determinada. Diazepam diminuiu 50% a atividade da subunidade α2/3 da Na+,K+-ATPase no hipocampo, mas não alterou a atividade da enzima em córtex entorrinal. O efeito do diazepam foi prevenido por flumazenil, indicando que a diminuição da atividade da Na+,K+-ATPase envolveu a ativação dos receptores GABAA. Além disso, a baixa concentração de cloreto no meio de incubação aboliu a diminuição da atividade enzimática induzida por diazepam. Nossos dados sugerem que a enzima Na+,K+-ATPase no hipocampo é sensível a efeitos farmacológicos dos benzodiazepínicos por meio de mecanismos ativados por receptores GABAérgicos.
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Distribuição da proteína Fos no lobo temporal medial de ratos Wistar durante o medo condicionado ao contexto, luz e som / Fos distribution in the medial temporal lobe during context-, auditory- and light-cued conditioned fear in Wistar rats.

Gustavo Massaro Onusic 26 November 2010 (has links)
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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