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Kyle, Colin T., i Colin T. Kyle. "Cytoarchitectonically-Driven MRI Atlas of the Hippocampus and the Behavioral Impact of Neural Recording Devices: Addressing Methodological Concerns for Studies of Age-Related Change in Hippocampal Subfields". Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/625684.
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The hippocampal formation forms a circuit of cytoarchitectonically distinct subregions, and substantial evidence suggests each region makes unique computational contributions that support spatial and episodic memory. With aging, hippocampal subfields undergo unique neurobiological alterations, and primate in vivo work making use of both MR imaging and chronic neural recording devices has important links to changes seen in nonprimate animal models with aging (Thome et al., 2016; Yassa et al., 2011a; Yassa et al., 2010). While MRI offers a noninvasive way to study the hippocampal subfields, identifying hippocampal subregions without using post mortem histology is a challenge. When different research labs attempted to identify the hippocampal subregions using a single subject’s MRI, researchers showed significant disagreement in where to label different subregions (Yushkevich et al., 2015a). Alternatively, chronic neural recording devices offer an invasive solution to studying hippocampal subfields. However, it is currently not clear whether the mechanical trauma and foreign body response produced by neural recording devices disrupts neural circuits critical for behavior. Here, my colleagues and I address these issues with in vivo primate research. Chapter I provides a general introduction to the hippocampal circuits and changes observed in aging. Chapter II presents novel methods for construction of a histology-driven MRI atlas of nonhuman primate hippocampus that addresses accurate identification of hippocampal subfields in MR images. Chapter III presents empirical work that examines whether chronic neural recording devices targeted at the hippocampus affect recognition memory. Finally, Chapter IV provides a general discussion of both works in the context of the broader literature.
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Becker, Nadine. "Imaging activity-dependent structural and functional plasticity of hippocampal CA3-CA1 synapses". Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-101290.
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Stevenson, Cassie Hayley. "Investigating the role of the hippocampal formation in episodic and spatial memory". Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5632.
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This thesis aims to explore the two dominant functional roles of the hippocampal formation, in the relational encoding of episodic memory and the neural representation of allocentric space, using a combination of pharmaceutical manipulations and single-unit recording techniques in rodents. The first part of this thesis focuses on episodic-like memory, defined by the original episodic memory triad: ‘what-where-when’ (Tulving 1972), which enables the behavioural aspects of episodic memory to be tested in non-human animals. Permanent neurotoxic lesions of the hippocampus and it’s subregions were induced to assess their role in a putative episodic-like memory task developed by Eacott and Norman (2004). In view of the difficulties encountered in successfully demonstrating the temporal component of episodic-like memory in rats, this task tested integrated memory for ‘what-where-which’, where the temporal component (when) was replaced with another event specifier: context (on ‘which’ occasion). Disruption of the hippocampal circuitry led to a specific impairment in the integration of all three event components, whereas the associative recognition of any combination of these features in isolation was left intact. These results confirm the hippocampal dependence of this episodic-like memory task and further reveals the necessity of both CA3 and CA1, hypothetically due to the underlying autoassociative role of CA3 with CA1 functioning as the vital output pathway for this associated information and/or as a mismatch detector. There has been much debate over the inclusion of the temporal component and sceptics may argue that any such interpretations of task-dependence on episodic-like memory processing are invalid considering the requirement for temporal processing is absent. Due to the proposal that a temporal framework necessarily provides the foundation on which episodic memories are built, the second chapter focuses on the development of a suitable protocol in which integrated memory for the original ‘what-where-when’ episodic memory triad can be reliably tested. The other main function attributed to the hippocampus was brought to light by the fascinating revelation that it’s neurons selectively fire in different regions of an environment, termed ‘place cells’ (O’Keefe and Dostrovsky 1971). From the numerous publications resulting from this discovery it has emerged that place cells not only respond to the spatial features of the environment but are also sensitive to a multitude of non-spatial features. These characteristics support the logical assumption that the primary firing patterns of the hippocampus should underlie it’s main purported roles, leading to speculations that they reflect episodic memory processes. The second part of this thesis aims to examine the relationship between hippocampal cells and behaviour by extending the work of Ainge et al. (2007a), in which a subset of hippocampal place cells were found to encode both current and intended destination in a double Y-maze ‘win-stay’ task. The development of these ‘goal-sensitive’ cells were initially investigated during the learning phase of this task. An exciting pattern of results showed a strong positive correlation between the emergence of goal-sensitive firing and behavioural performance on the task, tempting speculations that these firing patterns may underlie spatial learning and future planning, necessary to support performance. To ensure these firing patterns were not a mere reflection of greater experience on the maze, a second study was conducted in which the task demands changed over set periods of days. A significant increase in the proportion of cells demonstrating goal-sensitive firing was revealed when the protocol shifted to incorporate the spatial memory demands of the ‘win-stay’ task, with all other parameters of the protocol remaining constant. These results support the theory that goal-sensitive firing patterns are specifically related to the learning and memory demands of the spatial task, not a result of increased exploration of the maze. The last of this series of studies assessed hippocampal-dependence of this task and revealed that bilateral hippocampal lesions induced an impairment in spatial ‘win-stay’ performance. Collectively, these experiments demonstrate that goal-sensitive firing of hippocampal cells emerge in line with behavioural performance in a hippocampal-dependent task and the emergence of these firing patterns are specific to the learning and memory demands of a spatial ‘win-stay’ protocol. The functional role of the hippocampus in allocentric spatial processing may thus underpin it’s function in episodic memory and potentially in the imagining and planning of future events, whereby the hippocampus provides a ‘space’ in which retrieved information can be integrated in a coherent context to support the fluent and flexible use of information. This hippocampal function would necessarily require visual information to be accessed, concerning the arrangement of landmarks and cues within the environment, in association with information regarding internal orientation and direction and this leads to the question assessed in the final part of this thesis of where this integration occurs. Based on anatomical evidence and the current literature, the postsubiculum, an input structure to the hippocampus, emerged as a potential site for the convergence of sensory cues into the internally generated head direction cell and place cell networks to enable hippocampal-dependent spatial processing. Thus, the effects of temporary pharmacological blockade of AMPARs and NMDARs in the postsubiculum were assessed on the encoding of spatial memory in an object recognition paradigm. The impairment revealed in the ability to recognise novel object-place configurations demonstrates a key role for NMDAR-dependent plasticity within the postsubiculum itself in the formation of allocentric spatial memory. In summary, the experimental results reported in this thesis further elucidate the critical role the hippocampal formation plays in spatial and episodic memory by combining evidence from cellular physiology and neuroanatomy to the behaving animal and extends these findings to discuss a more general role for the hippocampus in imagining both past and future events, in order to successfully navigate, learn and enable past experience to influence our intended future plans and decisions.
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Zhang, Pei. "Synaptic modifications in hippocampal CA3 pyramidal cells in an Alzheimer's mouse model". Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0628/document.
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L'encodage de la mémoire dépend de changements durables dans l'activité des circuits synaptiques dans un ensemble de neurones interconnectés. La région CA3 de l'hippocampe reçoit des informations directement ou indirectement (à travers le gyrus denté - GD) en provenance des structures corticales. Des données théoriques et comportementales ont montré que la région CA3 est importante pour l'encodage de la mémoire épisodique, en particulier au stade initial de l'acquisition, en développant vraisemblablement une représentation instantanée d'un contexte. Les neurones pyramidaux CA3 reçoivent une variété de connections afférentes, parmi lesquelles les fibres moussues (FM), les axones des cellules du gyrus denté. Ces connections synaptiqes ont attiré une attention par leurs propriétés morphologiques et fonctionnelles uniques. Malgré les nombreuses études comportementales et computationnelle, les liens entre plasticité des circuits CA3 et encodage de la mémoire ne sont pas bien compris.Le cadre général de ce projet de thèse se situe dans l'étude des mécanismes synaptiques de l'encodage de la mémoire épisodique dans des conditions physiologiques ainsi que dans un modèle de souris de la maladie d'Alzheimer (MA). En effet, la MA se caractérise à un stade précoce par une mémoire épisodique altérée, qui peut être associée à une dysrégulation de la plasticité des circuits CA3.À l'aide de techniques d'enregistrement électrophysiologique, nous avons d'abord exploré les modifications dans les circuits CA3 peu de temps (quelques heures) après conditionnement de la peur contextuelle chez les souris adultes C57Bl6j. Nous avons observé une augmentation de la fréquence des IPSC spontanés accompagnée de changements mineurs dans le nombre de filopodia issus des boutons synaptiques des FM, tandis que les EPSCs et les plasticités à court terme de ces synapses ne sont pas modifiés. Cependant, cette augmentation n'est peut observée 24 heures après l'apprentissage contextuel. Nous avons également tenté de modéliser de manière simplifiée les réseaux neuronaux GD-CA3, afin d'étudier si et dans quelle mesure les interneurones locaux dans la région CA3 contribuent à la précision de l'encodage de la mémoire. [...]Dans l'ensemble ce travail a révélé que la transmission inhibitrice des circuits locaux CA3 de l'hippocampe pourrait être importante dans l'encodage de la mémoire épisodique. Dans le modèle murin de la MA avec déficit de mémoire, il y a une réduction de la transmission GABAergique et des courants médiés par les KAR réduits cellules pyramidales de CA3. Finalement, avons observé une modification transcriptionnelle d'un certain nombre de gènes dans CA3, à des stades précoces de développement de la pathologie dans notre modèle de MA. Notre étude pourrait contribuer à la compréhension des mécanismes pathologiques précoces de la MA, au niveau synaptique ainsi qu'au niveau transcriptionnel, et fournir des idées nouvelles sur les mécanismes sous-jacents au codage rapide de la mémoire contextuelleMemory encoding is thought to proceed from durable changes in the activity of synaptic circuits to the storage of patterns of electrical events in a sparsely distributed ensemble of neurons. Located at the entry level of hippocampal circuitry, the CA3 region of hippocampus is thought to be important for episodic memory encoding, especially at the initial stage of acquisition, by presumably developing an instant representation of a context. CA3 pyramidal neurons receive a variety of diverse inputs, among which the mossy fiber (MF) inputs draw special attention for its peculiar structure and unique synaptic properties. However, the links between the plasticity of CA3 circuits and memory encoding are not well understood.This thesis project aimed to address the synaptic mechanisms of episodic memory encoding in physiological conditions as well as in a mouse model of Alzheimer's disease (AD).Using electrophysiological recording techniques, we first explored the changes in CA3 circuits shortly after one-trial contextual fear conditioning in adult C57Bl6j mice. We show that despite hardly any changes in filopodia number of MF terminals, an increase in spontaneous IPSC frequency can be registered, while the EPSCs and short-term plasticities of theses synapses are unaltered. However, this increase cannot be seen anymore 24 hours after the contextual learning. We also tried to do simplified computational modeling of the DG-CA3 neuronal networks, to investigate if and to what extent the local interneurons in CA3 region contribute to memory encoding precision.AD is characterized at an early stage by impaired episodic memory, which may involve dysregulation of the plasticity of CA3 circuits.In the next step, we searched for synaptic deficits in CA3 local circuit in the early stage of AD pathology, taking advantage of a familial AD mouse model: 6-month male APP/PS1 mice. We report that there is a reduction in spontaneous IPSC frequency in CA3 neurons together with decreased inhibitory charges of evoked events at MF-CA3 synapses, whereas the short-term plasticity of these synapses and intrinsic properties of CA3 neurons remain unaffected. Furthermore, there is a robust reduction in Kainate receptor (KAR) mediated currents at MF-CA3 synapses, and the same results can be obtained from PSKO mice too, suggesting that disturbed function of γ-secretase and NCad processing pathways might underlie the dysfunction of KARs at MF-CA3 synapses.Finally, to screen for changes on a transcriptome level, we performed RNA-seq with dissected CA3 tissue from APP/PS1 mice and found a list of up- and down-regulated genes at this early stage of AD. Moreover, we carried out ChIP-seq for a histone modification marker: H3K4me3, which has been shown to be directly related to one-trial contextual memory, and here we report that there is a concrete decrease in H3K4me3 levels at the promoter areas of various genes in CA3 neurons. However, these genes are not overlapping much with the down-regulated genes from RNA-seq result, suggesting that other epigenetic mechanisms might play more important roles in expressing early deficits in this AD mouse model.Taken together, we show that inhibitory innervations of hippocampal CA3 local circuits might be important for episodic memory encoding, and in early AD mouse model with memory deficits, there is reduced GABAergic transmission and reduced KAR-mediated currents in CA3 neurons, together with many active transcriptional regulations across the genome. Our study might contribute to the understanding of early AD pathologies at synaptic level as well as transcriptional level, and provide novel insights into the mechanisms underlying rapid encoding of contextual memory
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LICHERI, VALENTINA. "Modulation of Hyperpolarization-Activated Cation Currents (Ih) by Ethanol in Rat Hippocampal CA3 Pyramidal Neurons". Doctoral thesis, Università degli Studi di Cagliari, 2015. http://hdl.handle.net/11584/266622.
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It is well established that ethanol (EtOH), through the interaction with several
membrane proteins, as well as intracellular pathways, is capable to modulate many
neuronal function. Recent reports show that EtOH increases the firing rate of
hippocampal GABAergic interneurons through the positive modulation of the
hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels. This effect
might be consistent with the increase of GABA release from presynaptic terminals
observed in both CA1 and CA3 inhibitory synapses that leads the enhancement of the
GABAergic system induced by EtOH. The activation of HCN produced an inward
currents that are commonly called Ih. Ih play an important role for generating specific
neuronal activities in different brain regions, including specific sub-regions of the
hippocampal formation, such as CA1 and CA3 pyramidal neurons and hippocampal
GABAergic interneurons. The main physiologic effect mediated by HCN-induced Ih is
directed to the control of the neuronal resting membrane potential and action
potential (AP) discharge as well as dampen synaptic integration. Since robust Ih are
also present in CA3 glutamatergic neurons, I here investigated whether the action of
EtOH in the control of CA3 excitability can be correlated with its possible direct
interaction with these cation channels. For this purpose, patch-clamp experiments
were performed in CA3 pyramidal neurons from hippocampal coronal slices obtained
from male Sprague-Dawley rats. The data obtained demonstrated that EtOH is able to
modulate Ih in biphasic manner depending on the concentrations used. Low EtOH
concentrations enhanced Ih amplitude, while high reversibly reduced them. This
biphasic action induced by EtOH reflects on firing rate and synaptic integration. In
addition, in this reports it has been shown that EtOH modulates the function of HCN
channels through interfering with the cAMP/AC/PKA intracellular pathways, an effect
that is mimicked also by other endogenous compounds such as dopamine through D1
receptors activation. These data suggest that the HCN-mediated Ih currents in CA3
pyramidal neurons are sensitive to EtOH action, which at low or relevant
concentrations is able to increase or reduce their function respectively. Altogether
these data suggest a potential new mechanism of EtOH actions on hippocampal
formation and may help to better understand the depressant central activity showed
by this drug of abuse
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Canepari, Marco. "Intrinsic variability and short-term changes in synaptic transmission in the rat hippocampal CA3 region". Doctoral thesis, SISSA, 1999. http://hdl.handle.net/20.500.11767/4432.
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Kanak, Daniel James. "Influence of perforant path synaptic excitation on the initiation of hippocampal sharp-wave ripple activity in vitro". OpenSIUC, 2013. https://opensiuc.lib.siu.edu/dissertations/776.
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Sharp-wave ripples (SWR) generated in the CA3 subregion of the hippocampus (HC) during rest and sleep appear to coordinate memory consolidation to the neocortex (NC) by (1) reactivating small subsets of neurons (i.e. cell-assemblies) that encode recent waking experience and (2) propagating this information through the hippocampal formation. Although CA3 self-organizes SWRs in the absence of extrinsic inputs, cortical input to the HC conveyed by perforant path (PP) may influence SWR initiation nevertheless. Still, direct evidence that PP synaptic excitation can elicit SWRs is lacking, and it is unclear how this influence might compete or interact with self-organizing mechanisms. This dissertation tested the hypothesis that CA3's SWR pattern generator would self-organize its activity in the absence of PP input, but readily entrain to such input when present. Spontaneous SWRs (sSWR) occurred in slices prepared from the ventral portion of the mouse HC. Low-intensity electrical stimulation of PP afferents evoked short-latency field EPSPs in CA3 that were often followed by precisely timed evoked SWRs (eSWR). The network and single-cell characteristics of sSWRs and eSWRs were indistinguishable, indicative of a common patter generator. PP stimuli that followed sSWRs too closely usually failed to elicit eSWRs. Using a custom MATLAB/Simulink application to control PP stimulus timing during the ~250 ms sSWR refractory period revealed a statistically significant effect of stimulus delay (25, 50, 100, and 200 ms) on eSWR incidence, reaching a value of 0.72 (95% CI = [0.61, 0.81]) 200 ms after sSWR onset. In contrast, sSWR incidence at this time was much lower (95% CI = [0.015, 0.049]). Lesions targeting the direct PP input to CA3 substantially reduced eSWR incidence. In intact slices, eSWRs were readily evoked by stimulating the medial entorhinal cortex (MEC). In summary, PP input to CA3 from the MEC can initiate SWRs at times when self-organizing mechanisms generally cannot. Assuming sSWRs convey information to the NC, the ensuing refractory period might provide an opportunity for cortical feedback to reinforce the recently engaged cell-assembly. In the absence of such feedback, CA3 could revert to its default mode of self-organized replay.
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Dennis, Siobhan Dennis. "An investigation of the effects of oxygen glucose deprivation on glutamate receptor localisation within hippocampal CA3 pyramidal neurons". Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544384.
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Caiati, Maddalena Delma. "Activity-dependent regulation of GABA release at immature mossy fibers-CA3 synapses: role of the Prion protein". Doctoral thesis, SISSA, 2012. http://hdl.handle.net/20.500.11767/4719.
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In adulthood, mossy fibers (MFs), the axons of granule cells of the dentate gyrus (DG), release glutamate onto CA3 principal cells and interneurons. In contrast, during the first week of postnatal life MFs release -aminobutyric acid (GABA), which, at this early developmental stage exerts a depolarizing and excitatory action on targeted cells. The depolarizing action of GABA opens voltage-dependent calcium channels and NMDA receptors leading to calcium entry and activation of intracellular signaling pathways involved in several developmental processes, thus contributing to the refinement of neuronal connections and to the establishment of adult neuronal circuits. The release of GABA has been shown to be down regulated by several neurotransmitter receptors which would limit the enhanced excitability caused by the excitatory action of GABA. It is worth noting that the immature hippocampus exhibits spontaneous correlated activity, the so called giant depolarizing potentials or GDPs that act as coincident detector signals for enhancing synaptic activity, thus contributing to several developmental processes including synaptogenesis. GDPs render the immature hippocampus more prone to seizures. Here, I explored the molecular mechanisms underlying synaptic transmission and activity-dependent synaptic plasticity processes at immature GABAergic MF-CA3 synapses in wild-type rodents and in mice lacking the prion protein (Prnp0/0 mice).
In the first paper, I studied the functional role of kainate receptors (KARs) in regulating GABA release from MF terminals. Presynaptic KARs regulate synaptic transmission in several brain areas and play a central role in modulating glutamate release at adult MF-CA3 synapses. I found that functional presynaptic GluK1 receptors are present on MF terminals where they down regulate GABA release. Thus, application of DNQX or UBP 302, a selective antagonist for GluK1 receptors, strongly increased the amplitude of MF-GABAA-mediated postsynaptic currents (GPSCs). This effect was associated with a decrease in failure rate and increase in PPR, indicating a presynaptic type of action.
GluK1 receptors were found to be tonically activated by glutamate present in the extracellular space, since decreasing the extracellular concentration of glutamate with a glutamate scavenger system prevented their activation and mimicked the effects of KAR antagonists. The depressant effect of GluK1 on GABA release was dependent on pertussis toxin (PTx)-sensitive G protein-coupled kainate receptors since it was prevented when hippocampal slices were incubated in the presence of a solution containing PTx. This effect was presynaptic since application of UBP 302 to cells patched with an intracellular solution containing GDP S still potentiated synaptic responses. In addition, the depressant effect of GluK1 on GABA release was prevented by U73122, which selectively inhibits phospholipase C, downstream to G protein activation. Interestingly, U73122, enhanced the probability of GABA release, thus unveiling the ionotropic type of action of kainate receptors. In line with this, we found that GluK1 receptors enhanced MF excitability by directly depolarizing MF terminals via calcium-permeable cation channels. We also explored the possible involvement of
GluK1 in spike time-dependent (STD) plasticity and we found that GluK1 dynamically regulate the direction of STD-plasticity, since the pharmacological block of this receptor shifted spike-time dependent potentiation into depression. The mechanisms underlying STD-LTD at immature MF-CA3 synapses have been investigated in
detail in the second paper.
STD-plasticity is a Hebbian form of learning which consists in bi-directional modifications of synaptic strength according to the temporal order of pre and postsynaptic spiking. Interestingly, we found that at immature mossy fibers (MF)-CA3 synapses, STD-LTD occurs regardless of the temporal order of stimulation (pre versus post or viceversa). However, as already mentioned, while STD-LTD induced by positive pairing (pre before post) could be shifted into STD-LTP after blocking presynaptic GluK1 receptors, STD-LTD induced by negative pairing (post before pre) relied on the activation of CB1 receptors. At P3 but not at P21, endocannabinoids released by the
postsynaptic cell during spiking-induced membrane depolarization retrogradely activated CB1 receptors, probably expressed on MF terminals and persistently depressed GABA release in the rat hippocampus. Thus, bath application of selective CB1 receptor antagonists prevented STD-LTD.
Pharmacological tools allow identifying anandamide as the endogenous ligand responsible of activity-dependent depressant effect. To further assess whether STD-LTD is dependent on the activation of CB1 receptors, similar experiments were performed on WT-littermates and CB1-KO mice. While in WT mice the pairing protocol produced a persistent depression of MF-GPSCs as in rats, in CB1-KO mice failed to induce LTD. Consistent with these data, in situ hybridization experiments revealed detectable levels of CB1 mRNA in the granule cell layer of P3 but not of P21mice. These experiments strongly suggest that at immature MF-CA3 synapses STD-LTD is mediated by CB1 receptors, probably transiently expressed, during a critical time window, on MF
terminals.
In the third paper, I studied synaptic transmission and activity dependent synaptic plasticity at immature MF-CA3 synapses in mice devoid of the prion protein (Prnp0/0). The prion protein (PrPC) is a conserved glycoprotein widely expressed in the brain and involved in several neuronal processes including neurotransmission. If converted to a conformationally altered form, PrPSc can cause neurodegenerative diseases, such as Creutzfeldt-Jakob disease in humans. Previous studies aimed at characterizing Prnp0/0 mice have revealed only mild behavioral changes, including an impaired
spatial learning, accompanied by electrophysiological and biochemical alterations. Interestingly, PrPC is developmentally regulated and in the hippocampus its expression parallels the maturation of MF. Here, we tested the hypothesis that at immature (P3-P7) MF-CA3 synapses, PrPC interferes with synaptic plasticity processes. To this aim, the rising phase of Giant Depolarizing Potentials (GDPs), a hallmark of developmental networks, was used to stimulate granule cells in the dentate gyrus in such a way that GDPs were coincident with afferent inputs. In WT animals, the pairing procedure induced a persistent increase in amplitude of MF-GPSCs. In contrast, in Prnp0/0 mice, the same protocol produced a long-term depression (LTD). LTP was postsynaptic in origin and required the activation of cAMP-dependent PKA signaling while LTD was presynaptic and was reliant on G protein-coupled GluK1 receptor and protein lipase C downstream to G protein activation.
In addition, at emerging CA3-CA1 synapses of PrPC-deficient mice, stimulation of Schaffer collateral failed to induce LTP, known to be PKA-dependent. Finally, we also found that LTD in Prnp0/0 mice was mediated by GluK1 receptors, since UBP 302 blocked its induction. These data suggest that in the immature hippocampus PrPC controls the direction of synaptic plasticity.
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Zhang, Pei [Verfasser], André [Akademischer Betreuer] Fischer, Helene [Gutachter] Marie, Lionel [Gutachter] Dahan, Yoon [Gutachter] Cho i Christophe [Gutachter] Mulle. "Synaptic modifications in hippocampal CA3 pyramidal cells in an Alzheimer's mouse model / Pei Zhang ; Gutachter: Helene Marie, Lionel Dahan, Yoon Cho, Christophe Mulle ; Betreuer: André Fischer". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/1153607174/34.
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Retailleau, Aude. "Activités normales et pathologiques du réseau hippocampique chez le rat : implication des systèmes monoaminergiques". Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14405/document.
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Les représentations mentales, en particulier les représentations spatiales, sont étroitement associées à l'activation coordonnée de groupes de cellules dans l'hippocampe. Nous avons entrepris l'étude des propriétés et activités spontanées du réseau hippocampique (et plus particulièrement de la région CA3) afin de mieux en comprendre le fonctionnement, dans les situations normales et pathologiques. En effet, certaines pathologies neurodégénératives telle que la maladie de Parkinson serait potentiellement associées à des troubles cognitifs hippocampo-dépendants. Ainsi dans la première partie de ma thèse, nous avons caractérisé la dynamique temporelle des signaux excitateurs et inhibiteurs spontanés de l'hippocampe par une approche électrophysiologique in vitro sur tranches d'hippocampe mais aussi chez l'animal anesthésié grâce des enregistrements multi-unitaires multi-sites. Ces travaux nous a permis de mettre en évidence que les caractéristiques de la dynamique du réseau CA3 remplissent quelques critères essentiels au concept d'assemblées cellulaires. De plus, cette étude a mis en évidence les caractéristiques fonctionnelles de l'hippocampe chez l'animal normal. Ces résultats peuvent donc être utiles pour de futures études sur les pathologies hippocampo-dépendantes touchant le codage ou la mémoire spatiale telle que la maladie de Parkinson. Ainsi, dans la deuxième partie de ma thèse, nous avons étudié les altérations fonctionnelles du circuit hippocampique chez un modèle rat de la maladie de Parkinson. La maladie de Parkinson est une maladie neurologique qui affecte le système nerveux central et entraine des symptômes essentiellement moteurs. La cause est une dégénérescence des neurones dopaminergiques mais aussi noradrénergiques et sérotoninergiques. Cependant, en dehors des troubles moteurs, cette pathologie est aussi caractérisée par des troubles cognitifs notamment des déficits spatiaux. Notre projet a donc consisté à analyser les mécanismes par lesquels les déplétions monoaminergiques entraîneraient des troubles de l'apprentissage spatial. Ce travail a été réalisé chez le rongeur à l'aide d'une étude associant une approche comportementale et des enregistrements électrophysiologiques chez l'animal anesthésié mais aussi chez l'animal éveillé en comportement. Nous avons ainsi pu mettre en évidence des dysfonctionnements hippocampiques causés par des lésions contrôlées des différents systèmes mono-aminergiques (plus particulièrement dopaminergique et noradrenergique) impliqués dans la maladie de ParkinsonMental representations, especially spatial ones are closely related to correlated activity in cellular assembly in the hippocampus. In this work, we analyzed the properties and the spontaneous activity of the hippocampal network in order to unravel its functioning in normal and pathological conditions. Several neurodegenerative disorders such as Parkinson's disease seems to be also associated to cognitive disorder related to hippocampus dysfunction. We first characterized the temporal dynamic properties of spontaneous excitatory and inhibitory signal. We then studied the functional alteration of the hippocampal network in a rat model of Parkinson's disease using behavioral and electrophysiological investigations. Our work showed that controlled lesion of the various monoaminergic systems induced hippocampus dysfunction related to spatial disorientation.In the first part of my thesis, we characterized the temporal dynamic of excitatory and inhibitory signals with electrophysiological recordings in vivo on hippocampal slices but also in anesthetized animals with multi-units multi-sites recordings. These studies allowed us to highlight that dynamic of CA3 network meets the criteria of cells assembly concept. Moreover, we characterize the functional properties of hippocampus in physiological conditions. These results could be useful for further studies on hippocampo-dependant pathologies in the context of spatial coding and memory.Thus, in the second part of my work, we studied the functional alterations of hippocampal network in the context of Parkinson disease. This pathology is a neurodegenerative disease which affects the central nervous system and leads essentially to motor symptoms. The cause is the degeneration of dopamine neurons but also of noradrenalin and serotonin neurons. Nevertheless, this pathology is also associated to cognitive disorders notably a form of spatial disorientation. Our project consisted to analyze the mechanisms by which monoamines depletions led to spatial learning impairments. This work was realized on rats with a study combinating behavioral approach with electrophysiological recordings in anesthetized animals but also in awake animals. We showed that some monoamines depletions (and notably dopamine and noradrenalin depletions) led to spatial impairments in behavioral tasks correlated to a change in firing and coding of neurons of hippocampus
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Mercer, Audrey. "Hippocampal circuitry and characterisation of interneurones in the CA2 subfield of the rat hippocampus". Thesis, University College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420370.
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Zucca, Stefano. "Analysis of synaptic function of CA3 microcircuit in vivo using optogenetic tools". Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22127.
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L'hippocampe est une région du cerveau située dans le lobe temporal médian. Avec d'autres structures limbiques, l'hippocampe est impliqué dans des processus d'apprentissage et de mémorisation et possède un rôle crucial dans le traitement spatial de l'information. Les synapses de l'hippocampe formées entre les fibres moussues (fm) originaires du gyrus denté et les neurones pyramidaux de CA3 ont reçu une attention particulière, compte tenu de la position stratégique occupée par le gyrus denté à l'entrée de l'hippocampe. En outre les synapses fm- CA3 sont distinctes de la plupart des autres synapses excitatrices du système nerveux central par leurs propriétés morphologiques et physiologiques uniques. Cela soulève la question de savoir si ces propriétés uniques reflètent aussi un rôle fonctionnel unique dans le traitement de l'information effectué par cette synapse au sein du microcircuit de l'hippocampe. Malheureusement nous ne savons que peu de choses sur la façon dont les cellules granulaires modulent l'activité des neurones de CA3 dans le réseau intact in vivo (Henze et al, 2002 ; Hagena et Manahan - Vaughan, 2010, 2011). Le manque d'information est dû au fait que la manipulation classique des circuits neuronaux par des approches électriques, pharmacologiques et génétiques manque de précisions spatiale et temporelle in vivo. L'utilisation de la stimulation extracellulaire de fibres moussues peut conduire à l'activation polysynaptique de cellules pyramidales de CA3, qui peuvent ensuite contaminer les réponses enregistrées. Par ailleurs, l'utilisation de critères trop conservateurs peut conduire à l'exclusion des réponses provenant des fibres moussues «purs» aux propriétés méconnues (Henze et al., 2000). Toutefois, le développement récent et rapide de l’optogénétique dans les neurosciences a fourni de nouveaux outils offrant une sélectivité spatiale élevée (activation optique spécifique de la cellule), et une grande précision temporelle (à l'échelle de la milliseconde), permettant la dissection et l'étude des circuits neuronaux in vivo. L'objectif de ma thèse était de mieux comprendre les mécanismes et les conséquences physiologiques de la plasticité synaptique à court terme se produisant à la synapse formée entre les fibres moussues et les neurones pyramidaux de CA3 dans le cerveau de souris intact. La présente thèse se compose de deux parties principales. Dans la première partie, j'ai exploré de nouveaux outils optogénétiques dans le but de contrôler l'activité des cellules granulaires à l’aide d’impulsions de lumière. La stimulation optogénétique repose sur l'activation du canal ionique channelrhodopsin - 2 - lumière fermée ( ChR2 ) par une lumière bleue et induit des potentiels d'action sur une large gamme de fréquences de stimulation. J'ai aussi observé que la stimulation optique peut être utilisée pour déclencher la plasticité à court terme au niveau des synapses fm-CA3.Dans la deuxième partie j'ai affiné la méthodologie de stimulation optogénétique in vivo pour la caractérisation non invasive du fonctionnement synaptique des synapses fm- CA3. La fiabilité de la stimulation optogénétique d'une population neuronale génétiquement ciblée ainsi que la résolution d'une seule cellule obtenue en utilisant des enregistrements de cellules entières sont des étapes importantes vers une meilleure compréhension du rôle fonctionnel des fibres moussues dans le réseau de l'hippocampe in vivoThe hippocampus is a brain region located in the medial temporal lobe. Along with other limbic structures, the hippocampus is involved in learning and memory processes and has a crucial role in spatial information processing. Within the hippocampus synapses made between mossy fibers (mf) originating from the dentate gyrus and CA3 pyramidal neurons have received particular attention, given the strategic position occupied by the dentate gyrus at the entrance of the hippocampus. Moreover mf-CA3 synapses are distinct from most of other excitatory synapses in the central nervous system for their unusual morphological and physiological properties. This raises the question if these unique properties reflect a unique functional role in information processing carried out by this synapse within the microcircuit of the hippocampus. Unfortunately very little is known on how granule cells modulate the activity of CA3 neurons in the intact network in vivo (Henze et al., 2002; Hagena and Manahan-Vaughan, 2010, 2011). The paucity of information is due to the fact that classical manipulation of neuronal circuits using electrical, pharmacological and genetic approaches lack spatial and temporal precision in vivo. The use of bulk extracellular stimulation may lead to polysynaptic activation of CA3 pyramidal cells, which can subsequently contaminate putative mossy fibers synaptic responses measured in CA3 pyramidal cells. The use of overly conservative criteria on the other side may lead to the exclusion of “pure” mossy fibers responses with unexpected properties (Henze et al., 2000).However the recent and fast growth of optogenetics in neuroscience has provided new tools with high spatial selectivity (cell specific optical activation) and temporal precision (at the millisecond scale), allowing the dissection and investigation of neuronal circuits in vivo. The aim of my thesis was to gain insight into the mechanisms and the physiological consequences of short-term synaptic plasticity occurring at mossy fibers to CA3 pyramidal neurons synapses in the intact mouse brain. The present thesis consists of two main parts. In the first part I explored new optogenetic tools to control the activity of granule cells with pulses of light. Optogenetic stimulation, which relies on the activation of the light-gated ion channel channelrhodopsin-2 (ChR2) by blue light reliably induced action potentials over a wide range of frequencies of stimulation. I also found that optical stimulation can be used to trigger short term plasticity at mf-CA3 synapses. In the second part I refined optogenetic stimulation methodology in vivo for non-invasive characterization of synaptic functioning of the mf-CA3 synapses. The reliability of optogenetic stimulation of a genetically targeted neuronal population together with the single cell resolution obtained using whole-cell recordings are important steps towards a better understanding of the functional role of the mossy fibers in the hippocampal network in vivo
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Malezieux, Meryl. "Dynamique intracellulaire des cellules pyramidales de CA3 dans l'hippocampe pendant les états de veille". Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0317/document.
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Les états de veille sont composés d’états cérébraux distincts, corrélés avec différents comportements et caractérisés par des oscillations spécifiques observables dans le potentiel de champ local (Local Field Potential, LFP). Bien que les différents états cérébraux et leur signature dans le LFP aient été caractérisés, les mécanismes cellulaires sous-jacents restent à ce jour peu connus. Des changements des propriétés de neurones uniques seraient corrélés avec, et pourraient participer à la génération de ces changements d’états cérébraux. L’activité coordonnée et synchronisée de neurones facilite certains processus cognitifs tels que la mémoire. L’hippocampe joue un rôle essentiel dans les mémoires spatiale et épisodique, et dans l’hippocampe, CA3 est important pour la formation d’associations facilitant l’encodage rapide de la mémoire. De plus, les informations provenant du cortex entorhinal, du gyrus denté, et de CA3 même sont comparées et intégrées dans CA3 avant d’être transmises à CA1. Lors de périodes de repos, le LFP hippocampique présente une activité large et irrégulière (Large Irregular Activity, LIA), ponctuée par des oscillations plus rapides, les sharp-wave ripples, jouant un rôle dans la consolidation de la mémoire. Lors de périodes exploratoires, le LFP hippocampique oscille aux fréquences theta (6-12 Hz) et gamma (30-100 Hz). Les cellules pyramidales (CP) de CA3 jouent un rôle important dans chacun de ces états ; elles sont nécessaires pour les sharp wave lors de périodes de repos, et les oscillations gamma lors de comportements exploratoires. Dans le but d’étudier les modulations intracellulaires des CP de CA3, nous avons réalisé des enregistrements de patch-clamp en configuration cellule entière chez l’animal éveillé. Nous avons associé ces enregistrements avec des mesures du diamètre pupillaire et de la vitesse de locomotion de l’animal, ainsi qu’avec l’enregistrement de l’activité oscillatoire du LFP dans l’hippocampe. Nos résultats montrent que certaines CP de CA3 sont sensibles à la modulation intracellulaire lors de différents rythmes hippocampiques, et ont tendance à diminuer leur potentiel de membrane moyen, leur excitabilité, leur variance et leur décharge de potentiel d’action lors des oscillations theta par rapport aux périodes de LIA. De futures études permettront de déterminer si ces changements sont dus à des changements d’entrées synaptiques et/ou de neuromodulateurs. Ces modulations pourraient jouer un rôle dans l’émergence des rythmes oscillatoires du LFP, et permettre à CA3 de réaliser différentes fonctions mnésiques à différents momentsWakefulness is comprised of distinct brain states, correlated with different behaviors and characterized by specific oscillatory patterns in the local field potential (LFP). While much work has characterized different brain states and their LFP signatures, the underlying cellular mechanisms are less known. Changes in single cell properties are thought to correlate with and possibly result in these changes in brain state. Synchronized and coordinated activity among distributed neurons supports cognitive processes such as memory. The hippocampus is essential for spatial and episodic memory, and within the hippocampus, area CA3 is important for rapid encoding of one-trial memory. Additionally, CA3 is the site where information from the entorhinal cortex, dentate gyrus, and CA3 itself is compared and integrated before output to CA1. During quiet wakefulness, the hippocampal LFP displays large irregular activity (LIA) punctuated by sharp-wave ripples, which play a role in memory consolidation. During exploratory behaviors, hippocampal LFP oscillates at both theta and gamma frequencies. CA3 pyramidal cells (PCs) play an important role in each of these brain states; they are necessary for both sharp waves during quiet wakefulness and for gamma oscillations during exploratory behavior. We explored the changes that occur in the intracellular dynamics of CA3 PCs during changes in brain state, by using whole-cell patch-clamp recordings from CA3 PCs in awake head-fixed mice. We combined those recordings with measurements of pupil diameter, treadmill running speed and LFP recordings of oscillatory activity. Our findings show that some CA3 PCs are prone to intracellular modulation during brain rhythms, and tend to decrease their average membrane potential, excitability, variance and output firing during theta as compared to LIA. Future studies will demonstrate whether these effects are due to changes in synaptic and/or neuromodulatory inputs. This modulation at the single-cell level in CA3 could play a role in the emergence of oscillations, and underlie the ability of CA3 to perform different memory functions during different brain states
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Pierson, Jamie L. "DORSAL HIPPOCAMPUS INFUSIONS OF CNQX INTO THE DENTATE GYRUS DISRUPT EXPRESSION OF TRACE FEAR CONDITIONING". Miami University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=miami1355165370.
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Maimaiti, Shaniya. "INSULIN ACTIONS ON HIPPOCAMPAL NEURONS". UKnowledge, 2017. http://uknowledge.uky.edu/pharmacol_etds/20.
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Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved in learning. The possible effects of insulin on learning and memory in young and aged rats were studied. In addition, the effects of insulin on the Ca2+-dependent afterhyperpolarization in CA1 pyramidal hippocampal neurons from young and aged animals were compared. Further, primary hippocampal cultures were used to examine the possible effects of insulin on voltage-gated Ca2+ channel activity and Ca2+-induced Ca2+-release; mechanisms known to influence the AHP.
We found that intranasal insulin improved memory in aged F344 rats. Young and aged F344 rats were treated with Humalog®, a short-acting insulin analog, or Levemir®, a long-acting insulin analog. The aged rats performed similar to young rats in the Morris Water Maze, a hippocampal dependent spatial learning and memory task. Electrophysiological recordings from CA1 hippocampal neurons revealed that insulin reduced the age-related increase in the Ca2+-dependent afterhyperpolarization, a prominent biomarker of brain aging that is associated with cognitive decline. Patch clamping recording from hippocampal cultured neurons showed that insulin reduced Ca2+ channel currents. Intracellular Ca2+ levels were also monitored using Fura-2 in response to cellular depolarization. Results indicated that a reduction in Ca2+-induced Ca2+-release from intracellular stores occurred in the presence of insulin.
These results suggest that increasing brain insulin levels in aged rats may have improved memory by reducing the AHP and intracellular Ca2+concentrations. This study indicates a possible mechanism responsible for the beneficial effects of intranasal insulin on cognitive function absorbed in selective Alzheimer’s patients. Thus, insulin therapy may reduce or prevent age-related compromises to Ca2+ regulatory pathways typically associated with cognitive decline.
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Nasrallah, Kaoutsar. "Consequences of synaptic plasticity at inhibitory synapses in mouse hippocampal area CA2 under normal and pathological conditions". Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB089/document.
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L'hippocampe est une région du cerveau importante pour la formation de mémoire. Des études récentes ont montré que la zone CA2 de l'hippocampe, longtemps ignorée, joue un rôle clef dans certaines formes de mémoire et notamment dans la mémoire sociale. De plus, des études post-mortem ont révélé des altérations spécifiques à la région CA2 chez les patients schizophrènes. Cependant, l’implication des neurones de CA2 dans les circuits de l'hippocampe reste peu connu, tant dans des conditions physiologiques que pathologiques. En combinant pharmacologie, génétique et électrophysiologie sur tranches d’hippocampe de souris, nous avons étudié comment les neurones pyramidaux (NP) CA2 sont recrutés dans les circuits hippocampiques après des changements d’inhibition et comment le recrutement des NP CA2 pourrait moduler l’information sortant de l'hippocampe. D’autre part, nous avons examiné les altérations fonctionnelles de la zone CA2 dans le modèle murin Df(16)A+/- de la microdélétion 22q11.2, le facteur génétique de risque de schizophrénie le plus élevé. Dans la région CA2 de l’hippocampe, les synapses inhibitrices contrôle les afférences des collatérales de Schaeffer (CS) et expriment une dépression à long-terme (DLTi) unique qui dépendant des récepteurs delta-opioïdes (RDO). Contrairement aux synapses CS-CA1, les synapses excitatrices CS-CA2 n’expriment pas de potentialisation à long-terme après application des protocoles d'induction. Cependant, nous avons constaté que différents types d'activités induisent une augmentation durable de l’amplitude des potentiels post-synaptiques (PPS) évoqués aussi bien par une stimulation des CS que des afférences distales des NP CA2, et ceci via une modulation de la balance excitation/inhibition. Nous avons démontré que ces augmentations du rapport excitation/inhibition sont les conséquences directes de la DLTi RDO-dépendante. De plus, la DLTi permet le recrutement des NP CA2 par les NP CA3 alors qu’une inhibition intacte empêche complètement leur activation en réponse aux stimulations des CS. Par ailleurs, le recrutement des pyramides de CA2 par les CS après disinhibition activité-dépendante ajoute une composante polysynaptique (SC-CA2-CA1) au PPS monosynaptique (SC-CA1) dans les NP CA1 et augmente leur activité. De plus, l’inactivation des interneurones exprimant la parvalbumine à l’aide d’outils pharmacogénétiques, a montré que ces cellules inhibitrices contrôlent fortement l'amplitude du PPS et l’activité des NP CA2 en réponse à la stimulation des CS et qu’elles sont nécessaires à l'augmentation RDO-dépendante du rapport excitation/inhibition entre CA3 et CA2. Enfin, l'étude de la zone CA2 chez les souris Df(16)A+/- a révélé plusieurs modifications dépendantes de l'âge dont une réduction de l'inhibition, une altération de la plasticité du rapport excitation/inhibition entre CA3 et CA2 et une hyperpolarisation NP CA2. Ces modifications cellulaires peuvent expliquer les déficiences de mémoire sociale que nous observons chez les souris Df(16)A+/- adultes. L’ensemble de nos études a permis de mettre en évidence le rôle des neurones CA2 dans les circuits de l'hippocampe. Enfin pour conclure, nous postulons que le recrutement des neurones CA2 dans les réseaux neuronaux sous-tend des aspects particuliers de la fonction de l'hippocampeThe hippocampus is a region of critical importance for memory formation. Recent studies have shown that the long-overlooked hippocampal region CA2 plays a role in certain forms of memory, including social recognition. Furthermore, post-mortem studies of schizophrenic patients have revealed specific changes in area CA2. As yet, the role of CA2 neurons in the hippocampal circuitry remains poorly understood under both normal physiological and pathological conditions. By combining pharmacology, mouse genetics and electrophysiology, we investigated how CA2 pyramidal neurons (PNs) could be recruited in hippocampal circuits in mice hippocampal slices following an activity-dependent change in the strength of their inhibitory inputs. We further investigated how subsequent recruitment of CA2 PNs could modulate hippocampal output. Moreover, we examined the functional alterations of area CA2 in the Df(16)A+/- mouse model of the 22q11.2 microdeletion, a spontaneous chromosomal deletion that is the highest known genetic risk factor for developing schizophrenia. In area CA2, inhibitory synapses exert a powerful control of Schaffer collateral (SC) inputs and undergo a unique long-term depression (iLTD) mediated by delta-opioid receptor (DOR) activation. Unlike SC-CA1 synapses, SC-CA2 excitatory synapses fail to express long-term potentiation after classical induction protocols. However, we found that different patterns of activity persistently increase both the SC and the distal input net excitatory drive onto CA2 PNs via a modulation of the balance between excitation and inhibition. We demonstrated that increases in the excitatory/inhibitory ratio are direct consequences of the DOR-mediated iLTD. Interestingly, we found that the inhibition in area CA2 completely preventing CA3 PNs to activate CA2 PNs, and following iLTD, SC stimulation allows CA2 PNs to fire action potentials. Moreover, the recruitment of CA2 PNs by SC intra-hippocampal inputs after their activity-dependent disinhibition adds a delayed SC-CA2-CA1 response to the SC-CA1 monosynaptic post-synaptic potential (PSP) in CA1 and increases CA1 PN activity. Furthermore, pharmaco-genetic silencing of parvalbumin-expressing interneurons revealed that these inhibitory cells control the PSP amplitude and the firing of CA2 PNs in response to SC stimulation and are necessary for the DOR-mediated increase in excitatory/inhibitory balance between CA3 and CA2. Finally, we found several age-dependent alterations in area CA2 in Df(16)A+/- mouse model of the 22q11.2 microdeletion. These included a reduction in inhibition, an impaired activity-dependent modulation of the excitatory drive between CA3 and CA2 and a more hyperpolarized CA2 PN resting potential. These cellular disruptions may provide a potential mechanism for the social memory impairment that we observe in Df(16)A+/- adult mice. Altogether, our studies highlight the role of CA2 neurons in hippocampal circuitry. To conclude, we postulate that the recruitment of CA2 neurons in neuronal networks underlies key aspects of hippocampal function
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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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Bétourné, Alexandre. "Etude pharmacologique de la synapse Fibres Moussues / CA3 : rôles de la dynorphine, du zinc et des canaux KATP KIR6.2/SUR1 dans la mémoire contextuelle chez la souris". Toulouse 3, 2008. http://thesesups.ups-tlse.fr/419/.
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Cette thèse analyse l'implication de plusieurs éléments de la synapse Fibres Moussues (FM) / CA3-hippocampique dans la formation de la mémoire contextuelle chez la souris. La région CA3 de l'hippocampe est un véritable réseau auto-associatif qui participe à la création de souvenirs complexes, de type épisodique. Les FM, principales projections des cellules granulaires du gyrus denté sur les neurones du CA3, sont essentielles aux processus d'apprentissages et de mémorisation. Elles sont capables de libérer, en plus du glutamate (leur neurotransmetteur principal), de nombreux neuromodulateurs. 1- Les FM co-libèrent un peptide opioïde, la dynorphine, dont les récepteurs cibles, les récepteurs opioïdes Kappa (KOR), sont localisés sur les terminaisons présynaptiques des fibres. Par des injections pharmacologiques localisées dans la région CA3 d'agonistes et/ou d'antagonistes sélectifs, nous avons montré que l'activation pharmacologique des KOR immédiatement après un apprentissage dans le paradigme de peur conditionnée au contexte (CPC), supprimait la mémoire contextuelle chez la souris. Les KOR sont également une des nombreuses cibles modulées par le zinc vésiculaire, un neurotransmetteur atypique co-localisé avec le glutamate dans des vésicules spécifiques, et libéré par les FM. 2- Les travaux antérieurs de notre laboratoire ont montré que la chélation pharmacologique du zinc hippocampique perturbait l'acquisition et la consolidation de la mémoire contextuelle (Daumas et al. , 2004). Afin de répondre aux problèmes de spécificité posés par les chélateurs du zinc et de clarifier les rôles joués par cet ion, nous avons essayé d'invalider le gène codant le transporteur ZnT3, une protéine internalisant le zinc vésiculaire dans cette région. L'injection intra-tissulaire ou intracérébroventriculaire de siRNAs nus visant l'ARNm de ce transporteur n'a pas eu d'effets sur le comportement et les concentrations hippocampiques en zinc. Nous avons donc commencé à développer un protocole original d'administration des siRNAs: l'électropulsation in situ. 3- Finalement, nous avons étudié l'implication des canaux KATP Kir6. 2/SUR1 de la région CA3 dans la mémoire contextuelle. Ces canaux possèdent un site de liaison spécifique pour le zinc et ils participeraient au contrôle métabolique de la neurosécrétion des FM. .This work analyses the putative involvement of several actors of the mossy fibers/CA3 synapse in the processing of contextual memory in mice. The CA3 of hippocampus forms a structured autoassociative network thought to process complex learning and episodic-like memories. Mossy fibers (MF), the main excitatory projections from dentate gyrus granule cells to the CA3, are essential for driving the storage of informations. MF terminals contain high amounts of vesicular zinc co-released with glutamate. Zn2+ has been shown to play the role of an atypical neurotransmitter in the hippocampus and might be required for the processing of memory at MF/CA3 synapses. 1- The hippocampus contains high amounts of Dynorphin, an opioid peptide co-released with glutamate from mossy fiber synapses. We performed transient pharmacological modulation of MF presynaptic Kappa opioid receptors (KOR) using bilateral microinjections in the CA3. Single injections of a selective agonist, antagonist or both, were performed immediately after conditioning C57BL/6J mice in a fear conditioning paradigm (FC). The agonist specifically decreased context-induced response suggesting that CA3-KOR are involved in the early consolidation of contextual memory processing. Importantly, among many other targets, KOR are sensitive to zinc modulation. 2- Previous works in our laboratory have shown the involvement of zinc released by MF in contextual memory (Daumas et al. , 2004). In order to improve our knowledge on the role played by MF-Zn2+ in memory, we injected specific naked siRNAs targeting the ZnT3 transporter, a protein internalizing zinc in MF synaptic vesicles. Repeated injections of different siRNAs either in the dentate gyrus or in the lateral ventricles were nearly without effects on mice behaviour in the FC and failed to alter hippocampal zinc levels. Meanwhile, we adapted the well known electropulsation technique in order to introduce nucleic acids in restricted brain areas of adult mice under brief anaesthesia. We will apply this technique for the delivery of anti-ZnT3 siRNAs in future experiments. 3- Finally, we evaluated the involvement of hippocampal ATP-sensitive potassium Kir6. 2/SUR1 channels (KATP) in learning and memory. .
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Malerba, Paola, Giri P. Krishnan, Jean-Marc Fellous i Maxim Bazhenov. "Hippocampal CA1 Ripples as Inhibitory Transients". Public Library of Science, 2016. http://hdl.handle.net/10150/614980.
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Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.
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Gouny, Claire. "Propriétés morpho-fonctionnelles des neurones GABAergiques générés tôt dans la région CA1 de l'hippocampe adulte et en développement". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0378/document.
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Les neurones GABAergiques sont une composante majeure des réseaux neuronaux corticaux. Au cours du développement, les neurones GABAergiques pionniers générés aux stades les plus précoces de l’embryogénèse forment une sous-population de neurones « hubs ». Cependant, leurs propriétés et leurs fonctions à l'âge adulte restent inconnus. En combinant différentes techniques, nous montrons que ces neurones pionniers ont également une fonction « hub » dans la région CA1 en développement in vitro et qu’ils maintiennent une forte connectivité fonctionnelle pendant les périodes de veille calme chez la souris adulte in vivo. Ces neurones, peu actifs de façon spontanée chez l’adulte, sont préférentiellement recrutés pendant les activités calciques synchrones souvent associées aux oscillations de type « SWRs ». Ceci est compatible avec leur faible excitabilité intrinsèque, révélée par des enregistrements en courant-imposé. L’étude des connexions synaptiques afférentes des neurones pionniers de CA1 adulte, par optogénétique, révèle un schéma de connectivité remarquable avec des entrées synaptiques GABAergiques issues du septum et la quasi-absence d’entrées thalamiques. Localement, ces neurones reçoivent moins de courants postsynaptiques GABAergiques, témoignant d’une intégration différentielle dans le réseau GABAergique inhibiteur. Enfin, nous montrons qu’une majorité significative de ces neurones pionniers appartiennent à la famille des neurones à projection longue distance. En conclusion, nous montrons que les neurones GABAergiques pionniers sont prédéterminés à occuper une place remarquable dans l’organisation fonctionnelle et structurale de l’hippocampe tout au long de leur vieThe remarkable diversity of cortical GABAergic neurons is rooted, at least in part, in their embryonic origins. Adding to the spatial control of interneuron specification is a temporal schedule that has significant impact on their fate. In the CA3 region of the hippocampus, GABAergic cells born the earliest (ebGABA) form a sparse subpopulation acting as ‘hubs’ during development and surviving until adulthood. However, their properties and function in adulthood remain elusive. Using a combination of techniques, we demonstrate that ebGABA neurons also operate as “hubs” in the developing CA1 region in vitro and that they seem to maintain such remarkable functional connectivity into adulthood as observed during quiet rest in vivo. EbGABA display a lower spontaneous activity rate, as expected from their lower intrinsic excitability and are preferentially recruited during the synchronous calcium events previously shown to be associated with SWRs. EbGABA also display a remarkable synaptic connectivity scheme as they receive long-range GABAergic septal inputs but are almost excluded from thalamic afferents. Locally, they receive fewer spontaneous inhibitory postsynaptic currents, indicating a particular integration into local GABAergic circuits. Moreover, using combinatorial immunohistochemistry, we have shown that a majority of these ebGABA neurons are long-range projection GABAergic neurons. We conclude that, ebGABA cells are predetermined to become exceptional nodes in the functional and structural organization of the hippocampus, throughout their lifetime
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Samadi, Mahsa. "mGluR-dependent plasticity in hippocampal area CA2". Thesis, University of Bristol, 2018. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.761199.
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Robert, Vincent. "Hypothalamic control of hippocampal area CA2 activity". Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2539&f=17446.
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L’hippocampe est une structure cérébrale cruciale pour la mémoire et l’apprentissage. Ces fonctions sont assurées par l’activité coordonnée des neurones hippocampiques au cours d’oscillations au sein du réseau neuronal. Différents profils d’activité rythmique sont rencontrés dans l’hippocampe, notamment les oscillations theta et gamma ainsi que les « sharp wave ripples ». Toutefois, les mécanismes sous-jacents ne sont pas intégralement élucidés. En effet, plusieurs structures cérébrales connectées à l’hippocampe participent à la genèse de ces oscillations, cependant leurs contributions respectives demeurent méconnues. En particulier, le noyau supramammillaire hypothalamique (SuM) est une région fortement impliquée dans les oscillations theta qui afférente l’aire CA2, zone hippocampique longtemps négligée. De fait, la physiologie de cette connexion hypothalamo-hippocampique n’a jamais été examinée jusqu’à présent. Pourtant, de récentes études in vivo ont révélé un rôle de l’aire CA2 dans la genèse des « sharp wave ripples » et le codage spatial, suggérant de ce fait des contributions spécifiques de cette région aux fonctions hippocampiques. Ainsi, l’élucidation des mécanismes gouvernant l’activité de réseau de l’aire CA2, de son influence par les afférences du SuM et des conséquences sur les efférences hippocampiques sont nécessaires pour améliorer la compréhension des fonctions mnésiques de l’hippocampe. Afin de répondre à ces questions, nous avons combinés des approches histologiques, pharmacologiques, électrophysiologiques ex vivo, optogénétiques et chimiogénétiques sur tranches d’hippocampe de souris génétiquement modifiées. Cela nous a tout d’abord permis de caractériser les mécanismes associés aux oscillations gamma-mimétiques induites par l’agoniste cholinergique carbachol dans l’aire CA2, à l’échelle cellulaire et à celle du réseau neuronal. Lors de ce régime d’activité, nous avons mis en évidence que les neurones pyramidaux de CA2 déchargent des bouffées de potentiels d’action couplés à la phase de l’oscillation. Par la suite, nous avons prouvé que les neurones pyramidaux superficiels et profonds de CA2 reçoivent différents degrés d’excitation mono-synaptique et d’inhibition di-synaptique de la part des afférences du SuM. De plus, nous avons démontré que les afférences du SuM recrutent des interneurones en panier parvalbumine-immunopositifs qui contrôlent la précision temporelle des potentiels d’action émis par les neurones pyramidaux de CA2 via un processus d’inhibition anticipée. De surcroît, nous avons prouvé que l’inhibition recrutée par le SuM exerce un contrôle temporel sur la décharge des bouffées de potentiels d’action par les neurones pyramidaux de CA2 en présence de carbachol. Enfin, nous avons observé que l’activation des afférences du SuM au niveau de l’aire CA2 provoque une réduction prolongée d’activité dans l’aire CA1 en conditions de tonus cholinergique élevé. Ainsi, nos résultats mettent en exergue un rôle crucial du SuM dans le contrôle de l’activité de l’aire CA2 et ses conséquences sur les efférences de l’hippocampe. En conclusion, nous postulons que la connexion entre le SuM et l’aire CA2 sous-tend des aspects capitaux de la rythmogenèse hippocampique et des fonctions associéesThe hippocampus is a brain structure critically involved in learning and memory. These functions depend on the coordinated activity of hippocampal neurons during network oscillations. Different rhythmic patterns of activity exist in the hippocampus such as oscillations in the theta and gamma range as well as sharp wave ripples, however their underlying mechanisms are not fully understood. Indeed, several brain structures connected to the hippocampus participate in the generation of these oscillations, but their respective contributions remain elusive. Notably, the hypothalamic supramammillary nucleus (SuM) is strongly involved in theta oscillations and projects to the long-overlooked hippocampal area CA2. Even so, the physiology of this hypothalamo-hippocampal long-range input has never been investigated. Interestingly, recent in vivo studies have revealed a role of area CA2 in the generation of sharp wave ripples and spatial coding, suggesting specific contributions of area CA2 to hippocampal network function. Therefore, information regarding the mechanism governing network activity in area CA2, how it is influenced by SuM inputs and the consequences on hippocampal output is required to better understand hippocampal-dependent learning and memory. To address these questions, we combined histology, pharmacology, ex vivo electrophysiology, optogenetics and chemogenetics on acute hippocampal slices from genetically-engineered mouse lines. This first allowed us to characterize the cellular and circuit mechanisms of gamma-like oscillations induced by the cholinergic agonist carbachol in area CA2. In this regime, we found that CA2 pyramidal neurons fire bursts of action potentials that show phase-coupling to the oscillation. Next, we proved that SuM inputs differentially drive mono-synaptic excitation and di-synaptic inhibition onto deep and superficial CA2 pyramidal neurons. In addition, we demonstrated that parvalbumin-expressing basket cells are strongly recruited by SuM inputs and control the timing and precision of CA2 pyramidal neurons action potential firing via feedforward inhibition. Moreover, we showed that the SuM inhibitory drive onto CA2 pyramidal neurons exerts a temporal control on their bursting of action potential in the presence of carbachol. Finally, we observed that activation of SuM inputs to area CA2 result in a prolonged reduction of activity in area CA1 under conditions of elevated cholinergic tone. Altogether, our results highlight a critical role of the SuM in controlling area CA2 activity and thereby influences the hippocampal output. To conclude, we postulate that the SuM to area CA2 connection underlies key aspects of hippocampal rhythmogenesis and associated functions
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Woodhall, Gavin Lawrence. "The role of glutamate receptors at the CA3/CA1 Schaffer collateral/commissural synapse of rat hippocampus". Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295902.
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Mestrallet, C. A. "Homeostasis of dendritic spines in hippocampal CA1 cells". Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1335903/.
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Synaptic connections in the brain respond throughout their lives to the activity of incoming neurones, adjusting their biological properties to increment activity-dependent changes but also avoid run-away excitation or complete loss of transmission. To ensure synapses remain functional when inputs change over time, compensatory mechanisms, coined homeostatic plasticity, take place either globally or locally. The correlation between synaptic strength and dendritic spine size has been clearly established, and thus imaging dendritic spines under various activity conditions has become accepted as a valid way of studying homeostatic changes of postsynaptic strength. Many neurological diseases demonstrate abnormalities of dendritic spines, directly linking their properties to the efficient functioning of the network. Understanding how dendritic spines are regulated under global changes of network activity is important to unveil clues about how to tackle those deficits in disease. Studying morphology of dendritic spines requires intensive and careful analysis, and a substantial part of this work has been dedicated to finding an appropriate way to analyse the data. Dendritic spines showed a remarkably stable density in CA1 pyramidal neurones during the second week in vitro, when treatments altering plasticity or even deafferentation failed to modify the autonomous development. However, deafferentation carried out a week later decreased the overall spine density and increased spine head size, specifically in the area that normally receives inputs from the transected axons. The strong activity of the Schaffer collateral axons in organotypic slices results in enlarged spines in the apical compared with basal dendrites. This difference between pathways was abolished by inhibition of CaMKII. Activity-dependent and homeostatic plasticities are working intricately to maintain the network efficacy. They operate at a local level in an age-dependent manner and are differentially modulated by the CaMKII or PKA pathways.
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Weinhard, Laetitia. "Live-imaging of microglia and spines interactions". Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4067.
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Au cours de ma thèse, j'ai observé que la microglie est nécessaire à la maturation des circuits hippocampaux par la formation de boutons multi-synaptiques. J'ai également étudié la mécanique d'élimination des synapses, et observé que la microglie n'élimine pas directement les compartiments post-synaptiques. En revanche, elle contacte spécifiquement et rapidement certaines épines, en induisant un étirement de la tête de l'épine. Les petites épines sont préférentiellement contactées, et leur proximité avec les compartiments phagocytiques de la microglie suggère qu'elles pourraient être digérées sans être détachées du dendrite auquel elles appartiennent. Enfin, le système du complément n'est pas requis pour la reconnaissance ni les interactions entre microglie et épines, mais semble nécessaire à leur maturationDuring my thesis, I found that microglia is necessary for the maturation of hippocampalcircuits through the formation of multiple synapse boutons. I investigated how microgliacould mechanistically eliminate synapses, and found that microglia do not eliminate entirepost-synaptic spines but instead make fast and specific contacts that often result in spinehead stretching. Small, immature spines are preferentially targeted by microglia, and theirproximity to phagocytic compartment suggests that microglia could subtly erode themwithout to challenge their attachment to the dendritic shaft. Last, the complement system isnot necessary for recognition and interaction of microglia with spines, however seemsnecessary for proper maturation of post-synaptic spines
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Sutherland, Gary Ralph. "The Effects of Repetition and Sequence Length on Hippocampal Memory Trace Reactivation". Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194909.
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Patterns of hippocampal ensemble activity that occur during a spatial experience are reactivated during subsequent rest periods and slow wave sleep. Connections between active cells are thought to be strengthened, via long term potentiation (LTP), by repeated co-activation during experience, which suggests that the level of memory trace reactivation would increase proportionately with repetition. Alternatively, plasticity associated with memory formation, such as LTP-dependent place field expansion and the induction of activity-dependent immediate early gene, ARC, saturates after only a few laps, indicating that reactivation would plateau after a few repetitions. The length of the repeated sequence may also affect reactivation, since activation of a very short sequence can be repeated more frequently than a long sequence in a given time period. We studied how memory trace reactivation was affected by repetition and the length of the repeated sequence by observing the reactivated patterns of cell-pair correlations after a rat ran laps around a long circular track versus running more laps around a short track. On the shorter track, fewer cells had place fields, but they covered more of the track, resulting in generally stronger correlations among active cells. In addition, neuronal activity was recorded from dorsal and mid-ventral CA1. In mid-ventral CA1, there were fewer place fields in the environment but they were larger, with generally stronger correlations among active cells. The comparison between dorsal and mid-ventral regions is thus analogous to the comparison between the sequence of place fields on a long versus short track, respectively. Although there were more cells active in the dorsal region, but more potent correlations in the middle region, no differences in memory trace reactivation were found with respect to repetitions, track length or hippocampal region. This suggests that although spatial scaling increased along the dorsoventral axis of the hippocampus, reactivation is balanced, and possibly coherent across the hippocampal axis and it is relatively independent of sequence length or number of repetitions, at least when that number exceeds about 20.
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Stockley, Edward William. "Three-dimensional reconstruction and electronic modelling of CA1 hippocampal neurones". Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295927.
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Guimond, Damien. "Les signaux extracellulaires modèlent la transmission GABAergique dans l'hippocampe en développement : le cas de la leptine". Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4030/document.
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La présente thèse est liée à l'étude des indices externes au réseau neuronal et comment ceux-ci impactent le développement du système nerveux central. Spécifiquement, notre objectif était d'explorer l'effet de la leptine, une hormone sécrétée par les adipocytes, sur la plasticité développementale GABAergique. Nous avons utilisé des tranches aigues d'hippocampe de rat nouveau-né pour montrer que la leptine induit une potentialisation de la fréquence de l'activité miniature GABAergique, nécessitant une augmentation postsynaptique de calcium et l'activation de voies de signalisation spécifiques. Nous avons confirmé cet effet sur des cultures de neurones hippocampiques, sur lesquelles nous avons commencé à développer une méthode pour mesurer le corrélat morphologique de la plasticité fonctionnelle des synapses GABAergiques en culture. Cette approche suggère que la plasticité GABAergique induite par la leptine pourrait survenir à densité constante de récepteurs GABAA membranaires. La leptine induit donc une potentialisation de l'activité GABAergique dans les neurones hippocampiques en développement. Enfin, nous avons trouvé que les neurones pyramidaux de CA3 reçoivent une activité miniature GABAergique réduite chez des souris ob/ob ne produisant pas de leptine, suggérant que la leptine contribue au développement de la circuiterie GABAergique in vivo. Dans l'ensemble, les études que nous présentons apportent un éclairage nouveau sur le développement d'aires cérébrales dites de « haut niveau », dont nous avons observé qu'elles intègrent des signaux dits de « bas niveau », c'est-à-dire en provenance de la périphérie afin de modeler leur développementThe present dissertation tackles the larger question of how external cues impact the development of the central nervous system. Our specific aim was to explore the effect of leptin, an adipocyte-derived hormone, on GABAergic plasticity in the developing rodent hippocampus. We used acute hippocampal slices of newborn rats to show that leptin induces a long lasting potentiation of the frequency of miniature GABAergic activity. Using pharmacological tools we found that this event requires a postsynaptic increase in intracellular calcium as well as specific postsynaptic signaling pathways. To address the mechanistic action of leptin we confirmed the leptin-induced plasticity on hippocampal cultures and began to develop a method to measure the morphological correlate of GABAergic synapses in culture. Applying this method suggested that the leptin-induced GABAergic plasticity might occur with a constant density of postsynaptic GABAA receptor puncta. Taken together, these data show that leptin induces a potentiation of GABAergic activity in developing hippocampal neurons, perhaps by recruiting clusters of GABAA receptors expressed at the membrane to form newly functional GABAergic synapses. In addition we found that CA3 pyramidal neurons of leptin-deficient ob/ob mice exhibit lower miniature GABAergic activity compared to wild type littermates, which suggests that leptin contributes to the development of the hippocampal GABAergic circuitry in vivo. Overall, these studies shed a new light on the development of admittedly "higher-level" cerebral regions which were found here to integrate "lower-level", peripheral signals to shape their development
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Weston, Ghabiba [Verfasser], i Alessio [Akademischer Betreuer] Attardo. "The effects of stress on in vivo hippocampal CA1 synaptic dynamics and hippocampal learning and memory / Ghabiba Weston ; Betreuer: Alessio Attardo". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1202011853/34.
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Gasselin, Célia. "Plasticités hebbienne et homéostatique de l'excitabilité intrinsèque des neurones de la région CA1 de l'hippocampe=hebbian and homeostatic plasticity of intrinsic excitability in hippocampal CA1 neurons". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5047.
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Pendant des décennies, la plasticité synaptique a été considérée comme le substrat principal de la plasticité fonctionnelle cérébrale. Récemment, plusieurs études expérimentales indiquent que des régulations à long terme de l’excitabilité intrinsèque participent à la plasticité dépendante de l’activité. En effet, la modulation des canaux ioniques dépendants du potentiel, lesquels régulent fortement l’excitabilité intrinsèque et l’intégration des entrées synaptiques, a été démontrée essentielle dans les processus d’apprentissage. Cependant, la régulation, dépendante de l’activité, du courant ionique activé par l’hyperpolarisation (Ih) et ses conséquences sur l’induction de futures plasticités reste à éclaircir, tout comme la présence d’une régulation de conductances dépendantes du potentiel dans les neurones inhibiteurs. Dans la première partie de ma thèse, nous caractérisons les mécanismes d’induction et d’expression de la plasticité à long terme de l’excitabilité (LTP-IE) dans les interneurons en panier de la région CA1 exprimant la parvalbumine. Dans une seconde partie, le rôle de Ih dans la régulation homéostatique de l’excitabilité neuronale induite par des manipulations de l’activité neuronale dans sa globalité a été étudié. Dans la troisième étude, nous montrons que la magnitude de la Dépression à Long Terme (LTD) détermine le sens de la régulation de Ih dans les neurones pyramidaux de CA1. En conclusion, cette thèse montre qu’à la fois dans les neurones excitateurs et inhibiteurs, les régulations des conductances dépendantes du potentiel aident à maintenir une relative stabilité dans l’activité du réseauSynaptic plasticity has been considered for decades as the main substrate of functional plasticity in the brain. Recently, experimental evidences suggest that long-lasting regulation of intrinsic neuronal excitability may also account for activity-dependent plasticity. Indeed, voltage-dependent ionic channels strongly regulate intrinsic excitability and inputs integration and their regulation was found to be essential in learning process. However, activity-dependent regulation of the hyperpolarization-activated ionic current (Ih) and its consequences for future plasticity remain unclear, so as the presence of any voltage-dependent conductances regulation in inhibitory neurons. In the first part of this thesis, we report the characterization of the induction and expression mechanisms of Long-Term Potentiation of Intrinsic Excitability (LTP-IE) in CA1 parvalbumin-positive basket interneurons. In a second part, the role of Ih in the homeostatic regulation of intrinsic neuronal excitability induced by global manipulations of neuronal activity was reported. In the third experimental study, we showed that the magnitude of Long-term Depression (LTD) determines the sign of Ih regulation in CA1 pyramidal neurons. In conclusion, this thesis shows that in both excitatory and inhibitory neurons, activity-dependent regulations of voltage-dependent conductances help to maintain a relative stability in the network activity
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Zarnadze, Shota [Verfasser]. "Gamma oscillation-induced plasticity in area CA3 of the hippocampus / Shota Zarnadze". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1082537136/34.
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Michon, Francois-Xavier. "Electrophysiologie de l’hippocampe in vivo pendant le comportement : étude de l'impact de la locomotion sur le potentiel de membrane des cellules pyramidales de CA1 de l'hippocampe chez la souris naviguant dans un environnement virtuel". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0476/document.
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La locomotion spontanée a une forte influence sur l’état du réseau hippocampique et joue un rôle crucial lors de l’intégration de l'information spatiale. Différents états d'attention ou de comportement au cours de l'éveil peuvent modifier la réponse des neurones aux stimuli sensoriels ainsi que les performances dans les tâches associées. Au cours du mouvement (mov.) le potentiel de champ local de l’hippocampe est caractérisé par des oscillations de fréquence thêta et les cellules pyramidales (CPs) présentent une décharge spécifique à la localisation de l'animal dans un environnement donné. Cependant, les déterminants intracellulaires liés à l'activation des cellules pyramidales de CA1 pendant du mov. sont peu connus. Dans ce travail de thèse, nous avons enregistré le potentiel de membrane (Vm) des CPs de CA1 chez des souris qui alternaient spontanément entre des périodes de mov. et des périodes d’immobilité lors d’une tâche de navigation spatiale virtuelle. Nous avons trouvé une modulation opposée du Vm entre les CPs de CA1 qui déchargeaient de manière régulière par rapport à celles qui déchargeaient en bouffées de potentiels d’action. Les cellules qui déchargeaient de manière régulière étaient plus dépolarisées et déchargeaient plus pendant le mov.comparé à l’immobilité. Les cellules déchargeant en bouffées de potentiels d’action, préférentiellement inhibées pendant les sharp wave-ripples, étaient hyperpolarisées de façon dépendante à la vitesse pendant le mov.. Cette inhibition dépendante de la vitesse pourrait permettre d’augmenter le rapport signal sur bruit afin de coder l’information spatiale de manière plus efficace pendant le movSpontaneous locomotion strongly influences the state of the hippocampal network and is critically important for spatial information coding. In neocortex, different attentional or behavioral states during arousal can modify neurons responses to sensorial stimuli and associated task performance. During locomotion, the local field potential of the hippocampus is characterized by theta frequency oscillations (5-12 Hz) and the pyramidal neurons present a specific discharge to the localization of the animal in environments. However, the intracellular determinants of CA1 pyramidal cells activation during locomotion are poorly understood. Here we recorded the membrane potential of CA1 pyramidal cells (PCs) while non-overtrained mice spontaneously alternated between periods of movement and immobility during a virtual spatial navigation task. We found opposite membrane polarization between bursting and regular firing CA1 PCs during movement. Regular firing CA1 PCs were more depolarized and fired at higher frequency during movement compared to immobility while bursting CA1 PCs, preferentially inhibited during sharp wave ripples, were hyperpolarized during movement in a speed dependent manner. This speed-dependent suppression of a subpopulation of CA1 PCs could enhance signal to noise ratio for efficient spatial coding during locomotion
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Bourboulou, Romain. "Spatial resolution of the cognitive map : investigation on the influence of proximal visual cues on spatial coding resolution in area CA1 of the dorsal hippocampus using virtual reality". Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0299.
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Pour naviguer de manière flexible et efficace dans leur habitat naturel, les mammifères peuvent s’appuyer sur une représentation interne du monde qui les entoure. L’hippocampe (HPC) est considéré comme l’un des acteurs de cette représentation car il contient des cellules de lieu. Lorsque l’animal se déplace, chacune de ces cellules s’active dans son champs de lieu et reste silencieuse ailleurs. Une question importante est de savoir si et comment la résolution spatiale de l’HPC dorsal peut s’adapter aux caractéristiques locales d’un même environnement. Nous avons exploré cette question en enregistrant l’activité de neurones de la région CA1 de l’HPC chez des souris effectuant des allers-retours dans un couloir virtuel. Des objets visuels 3D, des motifs sur les murs ou leur combinaison, ont été utilisés pour étudier leur impact sur la résolution du codage d’information spatiale. Nous avons observé que les objets améliorent la résolution du codage spatial dans leur voisinage. Les champs de lieu étaient plus nombreux, plus petits, avec une meilleure information spatiale et une meilleure stabilité. Ces effets étaient également observables instantanément suite à une manipulation des indices visuels. Ces résultats ont été confirmés au niveau de la population à l’aide d’un décodeur bayésien. Les objets ont également renforcé la résolution du codage temporel en améliorant la précession de phase. Nous proposons que la carte cognitive portée par les cellules de lieu de l’HPC pourrait avoir une résolution hétérogène pouvant être utilisée pour améliorer le codage et les inférences, notamment pour naviguer dans de grands environnementsTo flexibly and efficiently navigate in their natural habitat, mammals can rely on an internal representation of space, a cognitive map. The hippocampus is thought to be important for the elaboration of this map. It contains a peculiar type of cells: the place cells, which are active in specific parts of the environment (place fields) and virtually silent elsewhere. Place cell spatial coding can be more or less precise depending on the scale of the environment, the availability of sensory cues or their location along the septo-temporal axis of the hippocampus. However, whether and how place cells’ spatial coding resolution can adapt to local features of the same environment remains unclear. We explored this possibility by recording neurons in the dorsal CA1 area of mice navigating a virtual linear track. We used several types of visual information, such as 3D visual objects and 2D patterns on the walls or their combination to investigate their impact on spatial coding resolution. We observed that virtual objects improved spatial coding resolution in their vicinity. Place fields were more numerous, smaller, with better spatial information and stability. This effect was highly dynamic upon objects manipulations. Also, patterns on the wall led to an enhancement of spatial coding resolution, but to a lesser extent. These results were confirmed at the population level using a Bayesian decoder. Objects also strengthened temporal coding resolution through improved theta phase precession. We propose that the hippocampal place cells representation can have a heterogenous resolution, which could be used to improve coding or inference notably in large-scale environments
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Hulme, Sarah R., i n/a. "Heterosynaptic metaplasticity in area CA1 of the hippocampus". University of Otago. Department of Psychology, 2009. http://adt.otago.ac.nz./public/adt-NZDU20090818.161738.
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Long-term potentiation (LTP) is an activity-dependent increase in the efficacy of synaptic transmission. In concert with long-term depression (LTD), this synaptic plasticity likely underlies some types of learning and memory. It has been suggested that for LTP/LTD to act as effective memory storage mechanisms, homeostatic regulation is required. This need for plasticity regulation is incorporated into the Bienenstock, Cooper and Munro (BCM) theory by a threshold determining LTD/LTP induction, which is altered by the previous history of activity (Bienenstock et al., 1982). The present work aimed to test key predictions of the BCM model. This was done using field and intracellular recordings in area CA1 of hippocampal slices from young, adult male Sprague-Dawley rats. The first prediction tested was that following a strong, high-frequency priming stimulation all synapses on primed cells will show inhibition of subsequent LTP and facilitation of LTD induction (heterosynaptic metaplasticity). This was confirmed using two independent Schaffer collateral pathways to the same CA1 pyramidal cells. Following priming stimulation to one pathway, LTP induction was heterosynaptically inhibited and LTD facilitated. To more fully investigate whether all synapses show metaplastic changes, the priming stimulation was given in a different dendritic compartment, in stratum oriens, prior to LTP induction in stratum radiatum. This experiment supported the conclusion that all synapses show inhibited LTP following priming. A second prediction of the BCM model is that metaplasticity induction is determined by the history of cell firing. To investigate this, cells were hyperpolarized during priming to completely prevent somatic action potentials. Under these conditions inhibitory priming of LTP was still observed, and thus somatic action potentials are not critical for the induction of the effect. The next aim was to determine the mechanism underlying heterosynaptic metaplasticity. One way in which plasticity induction can be altered is through changes in gamma-aminobutyric acid (GABA)-mediated inhibition of pyramidal cells. For this reason, it was tested whether blocking all GABAergic inhibition, for the duration of the experiment, would prevent priming of LTP. However, priming inhibited subsequent LTP and it was concluded that GABAergic changes do not underlie either the induction, or expression, of the metaplastic state. Proposed revisions to the BCM model predict that postsynaptic elevations in intracellular Ca�⁺ determine the induction of metaplasticity. There are many potential sources for postsynaptic Ca�⁺ elevations, including entry through N-methyl-D-asparate receptors (NMDARs) or voltage-dependent calcium channels (VDCCs), or release from intracellular stores. Results of the present work demonstrate that the inhibition of LTP is dependent on the release of Ca�⁺ from intracellular stores during priming; however this release is not triggered by Ca�⁺ entry through NMDARs or VDCCs, or via activation of metabotropic glutamate receptors. Overall, the present results show that, in accordance with the BCM model, a high level of prior activity induces a cell-wide metaplastic state, such that LTD is facilitated and LTP is inhibited. In contrast to predictions of the BCM model, this is not mediated by cell-firing during priming. Instead the release of Ca�⁺ from intracellular stores is critical for induction of the metaplastic state.
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Allan, Jon. "Modelling the effects of serotonin on the hippocampal CA1 region during navigation". Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/9090/.
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The mammalian hippocampus is vitally involved in the formation of both episodic memory and semantic memory, and in learning and recognition. These functions are actively involved during spatial navigation through an environment. The rodent hippocampus in particular has been greatly studied, providing a wealth of experimental data; however collation of this data into universally accepted theories of hippocampal function is far from complete. The present study concentrates on events occurring in the rodent hippocampus during such navigation. There is particular emphasis on the hippocampal theta rhythm which is manifested during navigation; on the existence and characteristics of place fields and associated place cells; and on the phenomenon of phase precession. The study has been limited to the CA1 region. Testable assertions are made about these phenomena. These assertions have been incorporated into models which are described in the later chapters of the thesis. The model has been further extended to demonstrate features of serotonergic activity in the CA1 region.
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Florian, Cédrik. "Approches comportementales, pharmacologiques et moléculaires de l'étude de la région CA3 de l'hippocampe dorsal dans les apprentissages et les processus de consolidation de la mémoire spatiale". Toulouse 3, 2005. http://www.theses.fr/2005TOU30050.
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Cette thèse s'inscrit dans le cadre de la recherche sur les supports nerveux des activités cognitives liées à la connaissance de l'espace, et dans les formes de plasticité qui sont à la base de ces processus mnésiques. Comme de nombreux modèles computationnels confèrent à la région CA3 de l'hippocampe dorsal un rôle dans la mémoire spatiale et dans les processus de navigation, nous avons focalisé notre recherche sur cette région chez la souris C57BL/6. L'ensemble des résultats a montré que cette région est impliquée dans l'acquisition et surtout dans le traitement d'une information spatiale lors de la consolidation mnésique mais pas lors de la phase de rappel. De plus, ces études ont montré que les facteurs de transcription CREB, et les molécules d'adhésion cellulaire (PSA-NCAM) sont impliqués lors de la consolidation mnésique d'une information spatiale, certainement en agissant sur des modifications ou des réorganisations synaptiques au niveau de cette région CA3This work comes within the framework of research on the nervous support of cognitive activities in relation to the knowledge of the space, as well as the forms of plasticity which are the basis of these memory processes. This research work was focused on the dorsal hippocampal CA3-region study in C57BL/6 mouse because many computational models confer to this region a role in spatial memory and navigation processes. The combined results showed that this area is involved in the acquisition and particularly in the treatment of spatial information occuring memory consolidation, but not in the recall phase. Moreover, these studies showed that both CREB transcription factors and cellular adhesion molecules (PSA-NCAM) are involved during spatial memory consolidation, certainly by acting on synaptic modifications or reorganization in the CA3-region
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Francis, Kyle Andrew. "Measurement of the Feline Hippocampus Using Magnetic Resonance Imaging". The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306861337.
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Stevenson, Erica L. "Hippocampal Vasopressin 1b Receptors and the Neural Regulation of Social Behavior". Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1352472456.
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Bazelot, Michaël. "Origine des potentiels de champ unitaires et macroscopiques dans la région CA3 de l'hippocampe". Paris 6, 2011. http://www.theses.fr/2011PA066697.
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L’électroencéphalogramme (EEG) est largement utilisé comme mesure de l’activité des populations de neurones. Néanmoins, les mécanismes gouvernant se genèse restent peu connus. La première étude a confirmé que les cellules inhibitrices génèrent un champ monosynaptique détectable. Nous avons utilisé des faisceaux d’électrodes extracellulaires disposées le long du stratum pyramidale ou dans l’axe somato-dendritique des cellules pyramidales de CA3 afin d’étudier le patron spatial des événements. La technique de clusterisation par la méthode k-means nous a permis d'isoler l'activité d'interneurones innervant des zones distinctes de la membrane somato-dendritique ou d'interneurones innervant des zones périsomatiques diverses. La seconde étude a eu pour but de déterminer les altérations de la région CA3 de l’hippocampe des souris KO pour la doublecortine. Lorsque cette protéine est mutée chez la souris, la migration neuronale est désorganisée. Les tranches d’hippocampes issues des animaux KO sont spontanément épileptiques. Il se produit une augmentation de l’activité des interneurones, et ceux-ci semblent innerver à la fois les deux couches de cellules pyramidales. Nous avons enfin mis en évidence que les cellules pyramidales de CA3 sont également capables d’initier un potentiel de champ extracellulaire. Les mécanismes contribuant à la genèse des sharp-waves ne sont pas complètement connus. Nos données suggèrent que (1) les sharp-waves sont initiées au niveau de sites qui varient lors d’un enregistrement, (2) se propagent au sein même de CA3 et (3) comprennent des champs initiés par les interneurones périsomatiques de la région CA3
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Malik, Aqsa. "Functional characterization of T-type calcium channels in area CA3 of the hippocampus". Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55100.
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Calcium (Ca²+) entry through voltage-gated Ca²+ channels in dendrites of hippocampal pyramidal cells (PCs) contributes to synaptic depolarization and activation of downstream pathways that regulate many aspects of synaptic and cellular function. Activated by small depolarizing changes in voltage, T-type Ca²+ channels mediate low-threshold spikes (LTS) that drive the resting membrane potential towards action potential threshold. T-type Ca²+ channels are hypothesized to contribute to subthreshold synaptic depolarization in the CA3 subfield of the hippocampus due to the stratified nature of inputs on CA3 dendrites. While T-type Ca²+ channels are densely expressed in area CA3, their functional characteristics and interactions with postsynaptic receptors are not well understood and LTS have not been reported in CA3 PCs. In Chapter 3, using whole-cell electrophysiology, we demonstrate that LTS in CA3 PCs can be evoked by somatic current injection. LTS were only evoked when 4AP was applied to depress A-type K+ channels. Using specific pharmacological blockers, we show that Cav3.2 channels mediate LTS in CA1 and CA3 PCs. In Chapter 4, using two-photon Ca²+ imaging, we map the subcellular distribution of Cav3.2 channels in hippocampal PCs. Our results show that Cav3.2 channel expression is restricted to the soma and proximal dendrites in CA1 PCs, while Ca²+ influx from Cav3.2 channel activation occurs in distal (>50 μm) regions of CA3 PC dendrites. In Chapter 5, we demonstrate that mAChR stimulation potentiates LTS amplitude and such amplification of Ca²+ influx through Cav3.2 channels is dependent on M-current inhibition. Furthermore, we show that application of t-ACPD causes potent and rapid inhibition of LTS propagation. This inhibition occurs exclusively through mGlu₁ receptors and downstream activation of PKC is necessary for this process. Lastly, in Chapter 6, we show boosting of subthreshold synaptic signals by T-type Ca²+ channels in PCs within area CA3 but not CA1. Taken together, our data identify a new T-type mediated Ca²+ signaling pathway in CA3 PC dendrites that is unlocked by A-type K+ channel blockade, potentiated by mAChR activation, and inhibited by mGluR₁ activation. Furthermore, our study highlights the important involvement of T-type Ca²+ channels in enhancing dendritic depolarization in CA3 PCs.Medicine, Faculty of
Graduate
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Cohen, Ivan. "Activité de populations neuronales de l'hippocampe in vitro". Paris 6, 2002. http://www.theses.fr/2002PA066080.
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Baltan, Selva. "Long-term potentiation induced by temporary block of glycolysis in CA1 hippocampal neurons". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0016/NQ44609.pdf.
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Sumser, Martin Peter. "Calcium dependence of metabotropic glutamate receptor-mediated CREB phosphorylation in hippocampal CA1 neurons". kostenfrei, 2008. http://mediatum2.ub.tum.de/node?id=645338.
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Dos, Santos Carvalho Steve Francois. "Morpho-functional impact of Vangl2 on hippocampus development". Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0276/document.
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La Polarité Cellulaire Planaire (PCP) est une voie de signalisation originellement identifiée chez les invertébrés pour son rôle dans l’établissement d’une asymétrie cellulaire perpendiculaire à l’axe apico‐basal. Elle définit une polarité dans le plan d’un épithélium et coordonne cette polarité dans tout l'épithélium. L'activation de la voie PCP conduit à une réorganisation ducyto squelette en passant par une modulation des zones d'adhésion, régulant ainsi la forme et les mouvements des cellules. La voie de signalisation de la PCP est conservée tout au long de l'évolution jusqu'au mammifères, et contrôle la morphogénèse de divers tissus dont les tissus épithéliaux et mésenchymateux, ainsi que pour les tissues cardiaques, osseux, pulmonaire ou encore rénaux, mais aussi le système nerveux pour n'en citer que quelques‐uns.Afin d'identifier le rôle de vangl2, un des gènes centraux de la PCP, dans la mise en place de la circuiterie hippocampale, nous avons créé un modèle murin où vangl2 est supprimé de façon conditionnelle (cKO) dans le télencéphale à des stades précoces de l’embryogénèse. J’ai d'abord montré que Vangl2 est enrichi dans les neurones immatures de la zone sous granulaire du DG, ainsi que dans l’arborisation des neurites (axones et dendrites) des cellules granulaires (CG) du gyrus denté (DG) de l’hippocampe. Ainsi, Vangl2 est enrichi dans le stratum lucidum (sl), une région dense en contacts synaptiques entre le DG et le CA3. Dans cette région a lieu une synapse très particulière entre l'axone des CG, la fibre moussue (Mf) qui forme des boutons géants (MfB) et les excroissances épineuse (TE) issues de la partie proximale des dendrites apicaux. L'analyse structurale et ultra structurale de ces épines démontre que l'élargissement et la complexification de la synapse MfB/TE est bloquée dans nos mutants, alors que les zones actives (PSD) des épines sont présentes, mais réorganisées. De façon intéressante,dans une zone plus distale des dendrites des neurones du CA3 (sl), les épines sont, elles, plus grosses, suggérant un remodelage complexe du réseau en l'absence de vangl2. Enfin, j’ai pu montrer que ces défauts morphologiques étaient corrélés à des problèmes de mémoire complexe (mémoire déclarative) qui dépendent de l’hippocampe mais aussi du cortex. Cette étude montre pour la première fois l’importance du signal PCP dans maturation in vivo d’un circuit hippocampique spécifique ainsi que ces conséquences cognitives. D'autres résultats in vitro montrent que la suppression de vangl2 augmente la vitesse de déplacement des cônes de croissance sur des substrats de N‐cadhérine. J’ai utilisé la microscopie en super résolution spt‐PALM‐TIRF pour montrer que cette augmentation de croissance est inversement proportionnelle à la vitesse du flux rétrograde d’actine. Des expériences de FRAP permettent de suggérer que les molécules de N‐cadhérine engagées dans des interactions hémophiliques (adhésion) est plus importante dans les mutants vangl2 Je propose que Vangl2 contrôle le recyclage et la stabilité des protéines N‐cadhérine dans les sites d’adhésion afin de réguler localement les dynamiques d’actine et par conséquent la croissance neuronalePlanar Cell Polarity (PCP) is a signaling pathway originally known for its role in the establishment of cellular asymmetry perpendicular to the apico‐basal axis, in the plane of an epithelium. PCPsignaling has been shown to be crucial for many tissue patterning, including epithelial and mesenchymal tissue, but also cardiac, lung, bone, or kidney tissues, to cite a few. PCP signaling controls the regulation of cellular movement via the control of adhesion turnover and cytoskeleton reorganization. Vangl2 is one of the most upstream core PCP proteins that has been implicated in the recent years in various neuronal mechanisms, such as axonal guidance, dendrite morphogenesis or synaptogenesis. However, most of these studies rely on acute downregulation of the gene in vitro or in the use of a mouse presenting a spontaneous mutation of this gene, called Loop‐tail (Vangl2Lp) which causes the death of the embryo at birth. Moreover, the Vangl2Lp form of this protein has been described has a dominant‐negative form, making it difficult to untangle the molecular mechanism leading to the many phenotypes (included neuronal ones) reported inhomozygotes Looptail mice. To bypass this problem we created a conditional knockout (cKO) mouse in which vangl2 is deleted in the telencephalon during early embryogenesis. First, I analyzed the profile of expression of the protein during the first 3 weeks after birth, and I show that Vangl2 is specifically targeted to the arborization of granular cells (GC) of the dentate gyrus (DG) of the hippocampus, and excluded from cell bodies. Also, the protein was highly enriched in immature neurons of the subgranular zone of the DG, and in the stratum lucidum, a region of high‐density contacts between the GC and the CA3. In this region, a special type of synapse is formed: the Mossy Fiber Bouton (MfB) / Thorny Excrescence (TE) synapse. These synapses are bigger and more complex than conventional synapses. I then performed a structural and ultrastructural analysis of the DG/CA3 circuit in the Vangl2 cKO mice in order to understand the role of Vangl2 in the hippocampus maturation. For this, I used stereotaxic mice infection viruses, and Serial block face scanning electron microscopy (SBFsEM) with 3D reconstruction. Results show that in cKO mice, Mfs fasciculation is mildly impacted, and that the enlargement and complexification of the MfB/TE synapse is arrested, with TEs almost absent. I was able to link these morphological abnormalities to deficits in complex hippocampal‐dependent learning tasks. This work demonstrates for the first time the importance of PCP signaling for the in vivo maturation of a specific hippocampal circuit and its specific cognitive consequences. Next, I attempted to identify the functional consequences of vangl2 deletion on young hippocampal neuron maturation. My results confirm that Vangl2 is expressed in young hippocampal neurons and that the deletion of the gene affected neurite outgrowth on Ncadherin substrate. I used spt‐PALM‐TIRF super‐resolution microscopy to show that this increased neurite outgrowth was inversely proportional to a decrease in actin retrograde flowand to a decrease in the number of directed actin trajectories. These results strongly suggest that N‐cadherin adhesions are affected by Vangl2 deletion. FRAP experiments demonstratedthat in Vangl2 cKO neurons the recovery of N‐cadherin molecules engaged in homophilicbindings (adhesion) was decreased, suggesting that the turnover of N‐cadherin involved inadhesion is reduced. Altogether, I propose that Vangl2 controls the turnover/stability of Ncadherin proteins at adhesion sites to regulate local actin dynamics and consequently neuronal outgrowth
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Hinds, Heather L. 1969. "CaMKII at a central synapse : α-calcium/calmodium protien kinase II and synaptic plasticity at CA3 Schaffer collateral -- CA1 synapses in the mammalian hippocampus". Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/8300.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2001.Vita.
Includes bibliographical references (leaves 153-180).
Long term potentiation (LTP) of synaptic transmission at the CA3-CA1 hippocampal synapse is a model synaptic plasticity mechanism that may underlie hippocampal dependent learning and memory. Inhibition of post-synaptic calcium/calmodulin protein kinase II (CaMKII) has been shown to block LTP, and a global knockout of the highly expressed a isoform of CaMKII caused an impairment in LTP and hippocampus dependent learning. We examined the role of CaMKII in CA3-CA1 LTP by selectively deleting [alpha]-CaMKII in adult hippocampal CA1 or CA3 pyramidal cells using conditional gene targeting. With this approach, we could investigate the locus of change that underlies LTP expression, as both pre- (CA3) and post- (CA1) synaptic CaMKII dependent mechanisms have been implicated, and further examine how CaMKII dependent plasticity contributes to learning and memory in a background of normal brain development. CA3-CA1 LTP is reduced in CA1 [alpha]-CaMKII knockout mice, suggesting that post-synaptic CaMKII is required for normal LTP. These mice are strikingly reminiscent of the a-CaMKII global knockout mice, demonstrating comparable LTP impairments and abnormal behaviors. In contrast, CA3 [alpha]-CaMKII knockout mice have normal LTP at CA3-CA1 synapses, suggesting that CaMKII phosphorylation of pre-synaptic synapsin I is not required for LTP expression. Contextual and cued fear conditioning were also normal in CA3 mutants, demonstrating that one form of hippocampus dependent learning is intact.
(cont.) While several pre-synaptic short term plasticity mechanisms were unaffected in CA3 [alpha]-CaMKII knockout mice, repetitive stimulation protocols using short trains of stimuli of increasing frequency revealed enhanced frequency facilitation in mutants compared with controls. This suggests that CaMKII may be acting pre-synaptically as a negative regulator of neurotransmitter release during certain repetitive stimulation conditions, and as a "frequency detector" of calcium spikes, reaching higher levels of activation with increasing frequency of stimulation. Modulation of facilitation could be important to prevent synaptic terminals from depleting their vesicle stores during episodes of repetitive firing, or to maintain synaptic activity in an optimal range for information coding.
by Heather L. Hinds.
Ph.D.
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Maingret, Vincent. "Modulation de la plasticité synaptique par les prostaglandines E2 à la synapse fibre moussue/cellule pyramidale CA3 en conditions physiologiques et dans un modèle murin de la maladie d'Alzheimer". Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0313/document.
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La maladie d’Alzheimer (MA) est la forme la plus commune de démence chez les personnes âgées. La maladie se caractérise par des pertes de fonctions cognitives et plusieurs études ont montré une étroite relation entre la neuroinflammation, les déficits synaptiques et la perte des fonctions cognitives dans la MA. L'importance de la composante neuroinflammatoire a été démontrée essentiellement grâce à des données épidémiologiques rapportant une prévalence diminuée de 40 à 70% chez des patients traités chroniquement par des anti-inflammatoires non stéroïdiens (AINS) pour d'autres pathologies. Les AINS sont des inhibiteurs des enzymes de synthèse des prostaglandines. Les prostaglandines sont des métabolites de l’acide arachidonique. Parmi ces prostaglandines, la PGE2 est connue pour moduler la transmission et les plasticités synaptiques dans l’hippocampe et son expression est fortement augmentée dans la maladie d’Alzheimer. De nombreux travaux rapportent l'existence de déficits synaptiques dans la MA, notamment dans l'hippocampe, siège de la mémoire et de l’apprentissage. Ces travaux se sont focalisés sur les déficits postsynaptiques à la synapse archétypique formée entre les cellules pyramidales CA3 et CA1. A l'inverse, la synapse formée entre les fibres moussues et les cellules pyramidales CA3 (FM-CA3) exprime des plasticités présynaptiques atypiques, à court et à long terme, indépendantes des récepteurs NMDA et il n'existe que très peu d'études concernant ces plasticités dans le contexte de MA. L’objectif de cette étude a été de montrer l’implication de PGE2 dans les déficits synaptiques à la synapse FM-CA3 dans un modèle murin de la MA, la souris double transgénique APPswe/PS1ΔE9 (APP/PS1). Nos résultats montrent que l’application exogène de PGE2 chez des souris sauvages entraîne un déficit de plasticité uniquement sur la potentialisation à long terme (PLT) exprimée présynaptiquement via l’activation spécifique du récepteur EP3. Nous montrons aussi que dans la souris APP/PS1, seule cette PLT présynaptique est impactée à partir de 12 mois. Enfin, ce déficit de la PLT présynaptique pour la souris APP/PS1 est réversé par un inhibiteur spécifique des récepteurs EP3 montrant ainsi un rôle clé pour la signalisation PGE2 - EP3 dans les déficits synaptiques hippocampaux de ce modèle murin de la maladie d’AlzheimerAlzheimer’s disease (AD) is the most common form of dementia in elder people characterized by a loss of cognitive function linked to synaptic deficits. There is considerable evidence that neuroinflammation and AD are intimately linked. The key role of neuroinflammation in the course of the disease was figured out by epidemiological studies reporting a reduced prevalence to develop AD for patients chronically treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Prostaglandins are lipidic mediators derived from arachidonic acid and their synthesis is inhibited by NSAIDs. Among prostaglandins, PGE2 is known to modulate synaptic transmission and plasticity in the hippocampus and its concentration is higher in brains from AD patients. Numerous studies have reported synaptic deficits in the course of AD, mainly in the hippocampus which is essential for cognitive functions like learning or memory formation. The vast majority of these studies were focused on postsynaptic deficits at the canonical CA3-CA1 synapse. On the opposite, the synapse between mossy fiber and CA3 pyramidal cell (Mf-CA3) that express presynaptic short-term and long-term plasticity, was poorly studied in the context of AD. The aim of my project was to decipher the involvement of PGE2 in synaptic deficits in a mouse model of AD, the APPswe/PS1ΔE9 (APP/PS1). Our results show that acute application of PGE2 on wild type young mice impairs only presynaptic long term potentiation (LTP) at the Mf-CA3 synapse via the specific activation of EP3 receptor. In APP/PS1 mice, we demonstrate that the sole deficit at the Mf-CA3 synapse is an impairment of the presynaptic LTP at 12 months of age. Finally we demonstrate that the impaired presynaptic LTP in APP/PS1 mice can be rescued by the acute application of a specific EP3 receptor antagonist, pointing out the key role of PGE2 - EP3 signaling pathway in synaptic deficits in hippocampus in a mouse model of AD
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Longden, Kit. "Constraining the function of CA1 in associative memory models of the hippocampus". Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/770.
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CA1 is the main source of afferents from the hippocampus, but the function of CA1 and its perforant path (PP) input remains unclear. In this thesis, Marr’s model of the hippocampus is used to investigate previously hypothesized functions, and also to investigate some of Marr’s unexplored theoretical ideas. The last part of the thesis explains the excitatory responses to PP activity in vivo, despite inhibitory responses in vitro. Quantitative support for the idea of CA1 as a relay of information from CA3 to the neocortex and subiculum is provided by constraining Marr’s model to experimental data. Using the same approach, the much smaller capacity of the PP input by comparison implies it is not a one-shot learning network. In turn, it is argued that the entorhinal-CA1 connections cannot operate as a short-term memory network through reverberating activity. The PP input to CA1 has been hypothesized to control the activity of CA1 pyramidal cells. Marr suggested an algorithm for self-organising the output activity during pattern storage. Analytic calculations show a greater capacity for self-organised patterns than random patterns for low connectivities and high loads, confirmed in simulations over a broader parameter range. This superior performance is maintained in the absence of complex thresholding mechanisms, normally required to maintain performance levels in the sparsely connected networks. These results provide computational motivation for CA3 to establish patterns of CA1 activity without involvement from the PP input. The recent report of CA1 place cell activity with CA3 lesioned (Brun et al., 2002. Science, 296(5576):2243-6) is investigated using an integrate-and-fire neuron model of the entorhinal-CA1 network. CA1 place field activity is learnt, despite a completely inhibitory response to the stimulation of entorhinal afferents. In the model, this is achieved using N-methyl-D-asparate receptors to mediate a significant proportion of the excitatory response. Place field learning occurs over a broad parameter space. It is proposed that differences between similar contexts are slowly learnt in the PP and as a result are amplified in CA1. This would provide improved spatial memory in similar but different contexts.
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Park, Pojeong. "Calcium-permeable AMPA receptors are required for PKA-dependent LTP at hippocampal CA1 synapses". Thesis, University of Bristol, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.720854.
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Sandler, Vladislav M. "Origin and modulation of action potential evoked calcium signals in hippocampal CA1 pyramidal neurons". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0027/NQ38974.pdf.
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