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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.
11

Development of exctatory synaptic currents in mouse barrel cortex

Mierau, Susanna Barrett January 2003 (has links)
No description available.
12

The role of the hippocampal input/output pathways in objetc, spatial and temporal memory

Charles, David P. January 2004 (has links)
No description available.
13

Elucidating transcription factor driven molecular cascades involved in embryonic neurodevelopment

DeProto, Jamin January 2012 (has links)
The brain is an incredibly complex organ composed of many cell types with intricate morphology, connectivity, and electrophysiological properties. Transcription factors orchestrate this elaboration by regulating numerous sets of genes and, in effect, the initial partitioning of gross functional areas of the brain and the eventual terminal differentiation of individual cells. Much is known about the expression patterns of individual transcription , factors, however, elucidating the exact mechanisms of transcription factor function has been , difficult because of their indirect regulatory relationship with genetic targets. '. I There are a few established methods for detecting direct transcription factor genetic targets. Chromatin immunoprecipitation and conditional knock-out mouse models are the most commonly utilized methods. Although there are advantages to such methods, they are challenging to implement, expensive, and prone to artifact. Over-expression of an electroporated transcription factor in cultured brain is shown to be an effective alternative. Tbr2 and Er81 were studied using over-expression in embryonic mouse. Subsequent expression changes were detected using gene micro array. Tbr2 appears to primarily target genes involved with cell cycle and metabolism (i.e. AgI, Uspll, Cdk-l, and Hes) while Er81 notably regulated genes associated with terminal differentiation (i.e. SIc18a3, Layn, and K v3.1). These findings fit with suspected functional significance of these transcription factors. However, some surprising results suggested other, unexpected roles. Tbr2 appears to interact with a few prominent angiogenic genes (Fgfr1, Sema6D, Mapk6, Epha3, and Ctnnb1). It was found that Tbr2 expressing neuroprogenitors tend to associate with blood vessels and is suggestive of a novel relationship establishing a neurovascular-neuroprogenitor niche at least partly regulated by Tbr2 regulated genes. Additionally, Er81 appears to down- regulate Ctip2 and up-regulate Tshz2. Taken together, a mechanism begins to take shape where axonal projections within the cerebral hemispheres are increased by way of Er81 regulation of Ctip2 and Tshz2. Overall, these results show that the method can identify genetic targets of transcription factors and a useful tool for understanding mechanisms of development, including novel relationships between seemingly disparate cell types.
14

Transcriptional analysis of sex differences in hippocampal plasticity in the mouse

Sim es Martins, Ana Maria Raposo Antunes January 2006 (has links)
The neuronal representation of experience as stable memories requires a process termed consolidation, which engages the hippocampus. Sexual dimorphisms in the performance of a number of tasks requiring hippocampus-dependent memory formation have previously been described. These sex differences are generally attributed to gonadal hormone-mediated mechanisms which impact on neuroanatomy and modulate memory formation. At the molecular level, memory consolidation requires de novo transcription, activating the transcription factor CREB. This activation can be accomplished by a variety of signalling pathways including the CaM kinase cascade. Male mutant mice bearing a genetic deletion of CaMKK/, an element of this cascade, are impaired in spatial memory formation in the Morris water maze (MWM), and fail to activate CREB after spatial training. Remarkably, female mutants performed equally to their WT counterparts, indicating a sex-specific requirement for this kinase in spatial memory consolidation. This mutant line was used as a tool to investigate dimorphisms in the molecular mechanisms underlying memory formation. First, comparison of hippocampal transcriptional profiles between WT and CaMKK/ mutants by Affymetrix Microarray analysis identified four CaMKK/ regulated genes in males. Second, quantitative real-time PCR was used to compare hippocampal transcriptional profiles of these genes in naive males and females, and after training in two hippocampus-dependent tasks: the MWM and contextual fear conditioning (CFC). This study identified three genes with altered transcription thirty minutes after spatial training in the MWM and CFC in male mice: PSF, Gaa1 and SRp20. Naive females expressed lower levels of all three genes than naive males, and two of them (Gaa1 and SRp20) were not regulated specifically by training in these tasks at the same time point in females. The work described in this thesis has identified two male-specific molecular markers for hippocampal activity, and provided insights into sexual dimorphisms in the molecular mechanisms underlying memory consolidation.
15

Hippocampal function during conditional learning

Allen, Kevin January 2007 (has links)
We investigated whether the hippocampus plays an important role in conditional learning in rats. The effect of excitotoxic lesions of the hippocampus on the performance of non-spatial conditional discrimination tasks was tested. Hippocampal lesions impaired performance when lesions were made after learning or when goal boxes were used as stimuli. However, lesioned rats performed normally under other conditions, suggesting that the hippocampus is not essential to learn conditional discrimination tasks.
16

Structural molecular biology of proteins controlling cellular asymmetry

Walden, Miriam January 2011 (has links)
Cellular asymmetry plays a critical role in the development of multicellular organisms. In this thesis, the development of the Drosophila central nervous system (CNS) has been studied as a model for asymmetric localisation and cell division. Multipotent neuroblast (NB) stem cells of the CNS divide asymmetrically to produce all of the neurons and glial cells of the adult fly. During mitosis, the NB localises several protein and mRNA molecules to distinct compartments of the cell. The cell then divides asymmetrically along its apico-basal axis, segregating the localised molecules differently between the two daughter cells. One daughter cell inherits a set of molecules allowing it to continue to divide. The other inherits molecules that switch off cell division and switch on differentiation. Currently, the mechanisms which underlie this protein localisation and segregation are not well understood. In this thesis, a combination of molecular biology, biochemical, biophysical and structural approaches have been used to investigate the roles played by four proteins (Rab6, Inscuteable, Miranda and Prospero) in asymmetric protein localisation and cell division. Fragments of the Inscuteable, Miranda and Prospero proteins that interact with each other, have been designed, expressed in E. coli and characterised using chromatography and biophysical techniques. Preliminary analysis of the interactions between these protein fragments has been carried out. The proteins have also been subjected to crystallisation trials, in the hope of yielding crystals for structure determination. These have yet to produce diffracting crystals. The crystal structure of the Rab6 protein has been solved to 1.4 A and is currently the highest resolution Rab6 structure available. It is also the only structure of a Drosophila Rab protein to date.
17

Premotor and motor cortex and visually guided grasp : a methodological and experimental study of local field potentials in the cortex of the awake, behaving macaque monkey

Spinks, Rachel Lucy January 2005 (has links)
When we reach for and grasp an object, we must transport our hand to the correct location, shape it appropriately and subsequently grasp the object with an appropriate amount of force. This involves a complex series of neuronal computations to process the visual properties of the object, generate a desired action, and to finally relay instructions to the musculature of the hand and arm to execute the action. The premotor and primary motor cortices constitute an important part of this pathway. In the macaque monkey, the premotor cortex (F5) is known to receive visual and visuomotor information concerning the properties of graspable objects from the anterior intraparietal region (AIP). A strong reciprocal connection links F5 to the primary motor cortex (M1), from which the major descending output to the hand and arm muscles originates. This thesis is a study of local field potentials recorded in M1 and F5 during the performance of a reach to grasp task in the macaque monkey, and investigates their relationship to the task and to each other during two phases of the task; the observation of the object to be grasped, and the execution of the grasp. This study required the development of sophisticated techniques for the accurate localisation of recordings and for chronic recordings to be made with multiple electrodes in the two different cortical areas simultaneously. The use of MRI to aid localisation, and the use of an antimitotic solution that retards dural growth and thus allows long term multielectrode recordings are also described and validated.
18

Sensory induced long-lasting modification of spontaneous activity in the somatosensory cortex : electrophysiological and modelling studies

Phoka, Elena January 2012 (has links)
Emerging evidence suggests that spontaneous neocortical activity is not merely noise but can be modulated and/or engaged by sensory stimulation. We examined whether naturalistic sensory stimulation can induce specific long-term changes in spontaneous cortical state dynamics in the mouse somatosensory cortex, using both in vivo electrophysiology and modelling. Repetitive, high-frequency multi-whisker stimulation using sandpaper resulted in spontaneous ring rate increase of layer IV and Vb multi-units. The ring rate increase in these layers was sustained for at least 25 minutes following the stimulus. The ring rate increase was accompanied by an increase in layer IV sink amplitude. Increase in spontaneous activity was found also in excitatory single-units in layers IV and Vb. Neither the depth of anaesthesia nor stimulus-induced desynchronization could account for this effect. Finally, we found that elimination of lateral inputs, achieved by trimming away all but the principal whisker, abolished the effect. Single-whisker stimulation resulted in a decrease of activity in layers II/III, IV, Vb and VI, and was accompanied by a decrease in layer IV sink amplitude. In parallel, to study whether Spike-Timing-Dependent-Plasticity (STDP) can explain modifications in spontaneous synaptic dynamics, we developed a biologically inspired large-scale model of rodent barrel layers II, III and IV. Our model consists of approximately 4000 spiking neurons, 1.7 million synapses and 2.2 million dynamical variables. Repetitive sensory stimulation induced long-lasting changes in synaptic weights. The initial state of the network, described by a spontaneous attractor, shifted to a post-stimulus stable state following several repetitions of the same structured stimulation pattern. Furthermore, we found that STDP mediated modifications enabled our network to distinguish between structured and shuffled stimuli. Our experimental and modelling results show that sensory experience induces long-term modification of spontaneous activity in the somatosensory cortex. They suggest that lateral projections and time-dependent plasticity mechanisms play an important role in this process.
19

Caractérisation des vésicules extracellulaires (VEs) d’origine microgliale et mise en évidence de leur effet neurotrophique / Characterization of microglial extracellular vesicles and investigation of their neurotrophic potential

Arab, Tanina 18 January 2019 (has links)
Les cellules microgliales sont considérées comme les cellules immunitaires résidentes du système nerveux central (SNC). De nombreuses études ont démontré que ces cellules sont activées et recrutées sur le site de lésion. Les cellules microgliales de sangsue présentent un mode d’activation et de migration similaires post lésion expérimentale du SNC. Cette activation est accompagnée d'une libération massive de vésicules extracellulaires (VEs).Les VEs sont de petites particules produites par la plupart des types cellulaires et sont présentes dans plusieurs liquides biologiques, notamment la salive, l'urine, le lait maternel, le plasma et le liquide céphalo-rachidien ... Leur taille varie entre 30 nm et 1 µm de diamètre. Selon leur origine cellulaire, deux populations principales ont été décrites. Les exosomes qui sont connus comme des vésicules d'origine endosomales et les microvésicules qui sont générées suite au bourgeonnement de la membrane plasmique.Les travaux portent sur l'isolation de VEs libérées par des cellules microgliales en culture primaire. Chez la sangsue, ces dernières sont séparées des populations de neurones suite à la dissociation du SNC. Après quatre jours de culture, les VEs des cellules microgliales ont été isolées du milieu et leur contenu protéique a été analysé par spectrométrie de masse.D'autre part, les VEs isolées ont été également testées in vitro pour leur potentiel à induire une croissance neuritique à la fois sur les neurones de sangsue et des lignées cellulaires de neuroblastome de mammifères. / In Mammals, microglial cells are considered as the resident immune cells in central nervous system (CNS). Many studies demonstrated that, after injury, these cells are activated and recruited at the lesion site. Leech microglia presents a similar pattern of microglial activation and migration upon experimental lesion of its CNS. This activation is associated with the release of a large amount of Extracellular Vesicles (EVs). EVs are small particles produced by numerous cell types and found in several biological fluids including saliva, urine, breast milk, plasma and cerebrospinal fluid ... Their size fluctuates between 30 nm and 1 µm in diameter. Depending on their cell origin, two EVs populations are reported: exosomes are described to be endosomales vesicles, while microvesicles are generated after plasma membrane shedding. The main goal of this work was to isolate microglia EVs released in primery culture. For this purpose, microglial cells were separated from neurons after leech CNS dissociation. After four days, EVs were isolated from conditionned medium and their protein content was investigated by mass spectrometry analyses. In the other hand, EVs were assessed for their potential to induce neuritite outgrowth on both leech neurons and mammal neuroblastoma cell lines.
20

Étude des microARNs dans les vésicules extracellulaires microgliales : signatures et neuroprotection / Study of microRNAs in microglial extracellular vesicles : signatures and neuroprotection

Lemaire, Quentin 30 September 2019 (has links)
Dans le Système Nerveux Central (SNC), les cellules gliales influencent les activités neuronales. Les cellules microgliales, cellules immunitaires résidentes du SNC, contrôlent grandement l’état neuroinflammatoire. Ce contrôle est particulièrement important dans les fonctions physiologiques et s’avère souvent défectueux dans les neuropathologies. Les cellules microgliales sont en relation avec le microenvironnement cérébral et communiquent avec les autres types cellulaires (astrocytes, oligodendrocytes et neurones) afin de contrôler l’état neuroinflammatoire. Parmi les différents modes de communication intercellulaire au sein du SNC, les vésicules extracellulaires (VEs) interviennent largement dans les processus physiologiques (développement, homéostasie…) et pathologiques (maladies neurodégénératives…). C’est pourquoi, ce mode de communication a été étudié dans le dialogue entre la microglie et les neurones chez la sangsue Hirudo medicinalis. Cet annélide est un modèle intéressant de neurobiologie grâce à la structure linéaire de son système nerveux et à l’organisation de ses types cellulaires. Il permet l’étude du dialogue entre les cellules microgliales et les neurones au niveau d’une lésion expérimentale. Dans un premier temps, les résultats ont montré que les cellules microgliales interagissent avec les neurones lors d’une lésion du SNC et que des VEs sont libérées au niveau de cette lésion. De plus, les cellules microgliales produisent des VEs qui interagissent avec les neurones et délivrent un effet neurotrophique in vitro sur des neurones de sangsue et de rat. Dans un deuxième temps, la complexité des composés vésiculaires ainsi que des impératifs d’efficacité liés aux méthodes d’isolement nous ont conduits à développer l’analyse protéomique non ciblée et à grande échelle afin de valider les fractions positives en VEs mais aussi identifier leurs signatures protéiques biologiquement actives. Dans une dernière partie, nous nous sommes intéressés aux microARNs (miARNs) contenus dans les VEs microgliales. Les résultats ont permis l’identification de 6 miARNs dans les VEs microgliales, dont un seul, miR-146a, est décrit à ce jour dans le SNC chez les mammifères. Dans un contexte de dialogue neuroprotecteur entre VEs microgliales et neurones, les analyses neuronales ont prédit des ARNm potentiellement régulés par les miARNs contenus dans les VEs. Ces 6 miARNs ont également été identifiés dans les VEs issues de microglie de souris, de rat et humaine. Dans leur ensemble, les résultats montrent que les cellules microgliales chez la sangsue produisent des VEs, ayant un effet neurotrophique sur les neurones, y compris des neurones de rat. L’identification des molécules présentes dans ces VEs (protéines et miARNs) a permis de soulever des perspectives sur les mécanismes neuroprotecteurs supportant ce dialogue microglie-neurone qu’il sera intéressant d’examiner chez les mammifères dans un contexte de lésion nerveuse. / In the Central Nervous System (CNS), the glial cells influence neuronal activities. The microglial cells, resident immune cells of the CNS, greatly control the neuroinflammatory state. This control is particularly important in physiological functions and is often defective in neuropathologies. The microglial cell activities depend on the brain microenvironment and they communicate with other cell types (astrocytes, oligodendrocytes and neurons) to control the neuroinflammatory state. Among the different mechanisms of intercellular communication within the CNS, extracellular vesicles (EVs) play a major role in physiological processes (development, homeostasis, etc.) and pathological processes (neurodegenerative diseases, etc.). Therefore, this mode of communication was studied in the dialogue between microglia and neurons in the leech Hirudo medicinalis. This annelid is an interesting model of neurobiology thanks to the linear structure of its nervous system and the organization of its cell types. It allows the study of the dialogue between microglial cells and neurons at the level of an experimental lesion. At first, the results showed that microglial cells interact with neurons during CNS injury and that EVs are released at the level of this lesion. In addition, microglial cells produce EVs that interact with neurons and deliver a neurotrophic effect in vitro on leech and rat neurons. In a second step, the complexity of the vesicular compounds as well as efficiency requirements related to the isolation methods led us to develop the non-targeted proteomic analysis on a large scale in order to validate the positive EV fractions but also to identify their biologically active protein signatures. In a last part, we were interested in the microRNAs (miRNAs) contained in microglial EVs. The results allowed the identification of 6 miRNAs in microglial EVs, of which only one, miR-146a, is described to date in the mammalian CNS. In a context of neuroprotective dialogue between microglial EVs and neurons, the analysis of neuronal protein signatures predicted mRNAs potentially regulated by miRNAs contained in EVs. These 6 miRNAs were also identified in EVs derived from mouse, rat and human microglia. Overall, the results show that microglial cells in the leech produce EVs, exerting a neurotrophic effect on neurons, including rat neurons. The identification of the molecules present in these microglial EVs (proteins and miRNAs) made it possible to raise perspectives on the neuroprotective mechanisms supporting this microglia-neuron dialogue that will be interesting to examine in mammals in a context of nerve injury.

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