Development of the bi-hippocampal epileptic network in the kainate mouse model of temporal lobe epilepsy

Diplôme Master Development of the bi-hippocampal epileptic network in the kainate mouse model of temporal lobe epilepsy eng 2024 author Hernot Maëlle 908134 director Quairiaux Charles 640914 Structure enseignement (ENSI) director Michel Christoph 91629 Département de neurosciences fondamentales (NEUFO) director Friscourt Fabien 935036 Département des neurosciences cliniques (OTONO) Epilepsy ranks among the most prevalent neurological disorders, with temporal lobe epilepsy (TLE) being the predominant form of focal epilepsy. In TLE, seizures originate in a restricted pathological region, i.e. the epileptic focus (EF). Yet, TLE is associated with widespread morphological and functional network alterations extending beyond the EF, including remote interictal activity, suggesting the presence of an epileptic network (EN). Focal epilepsy is increasingly recognized as a dysfunction of large- scale brain networks, in which not only epileptic activity affects distributed networks but also, the other way around, remote regions are involved in the generation of epileptic activity. In this context, recent studies from our laboratory showed in the intra-hippocampal kainate mouse (IHK) model, a well- established model reproducing major aspects of TLE, the development of extra-focal regions that can produce pathological interictal activities and may participate in seizure initiation. The emergence and dynamics of large-scale network alterations, their underlying mechanisms, and the contribution of these networks to epileptic activity remain poorly understood. Altogether, it remains difficult to disentangle whether the remote alterations are due to the same initial insult that started epileptogenesis in the EF and maturate independently or whether they are driven progressively by EF activities.To address this question, we first used multisite intracerebral recordings (mSEEG) in the IHK mouse model to investigate the emergence of a type of pathological activity, i.e. bursts of spikes (SBs), in the EF and the contralateral hippocampus (CH) with high spatial and temporal resolution along the latent phase of the disease, i.e. the epileptogenesis period. Our findings indicate that SBs can be detected very soon after the SE in both regions but their appearance in terms of amplitude, duration and associated high-frequency oscillations (HFOs), display a progressive evolution along the latent phase. Secondly, to investigate the role of the EF and of the CH for the development of the EN and explore their mutual influence, we combined mSEEG with targeted chemogenetic inhibition, to reduce their activities during the critical phase of epileptogenesis. The current preliminary results, although indicative of certain trends, do not allow definitive conclusions to be drawn about the dynamics of the bi-hippocampal network, underlining the need for further analysis to decode the complex mechanisms and interactions within this network and their specific roles in the development of epilepsy. Dewey 616.8 Maîtrise universitaire interdisciplinaire en neurosciences 53 Département de neurosciences fondamentales 21A false 118 Organisation et plasticité des réseaux neuronaux cérébraux 148 dacaa0e7-e373-48cf-8741-95164a4f5922 Master thesis Restricted MasterThesis_MH.pdf 2486195 application/pdf 6982f56afc11b74da4a22e0d5473d8994f8d44f79651f515c3a47efb4cd1532d restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Development of the bi-hippocampal epileptic network in the kainate mouse model of temporal lobe epilepsy				2024	61	0

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Hernot, Maëlle

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