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Implication des circuits neuronaux du cortex somatosensoriel dans l’initiation de l’activité paroxystique de l’épilepsie absence

Abstract : Cortical neurons are organized in networks which allow complex functions. Abnormalities of neuronal connections composing these networks can lead to functional alterations and pathological activities as in some forms of epilepsy. Absence-epilepsy is characterized by non-convulsive generalized seizures associated with synchronous and bilateral spike-and-wave discharges (SWD) on electroencephalographic recordings and impairment of consciousness. Many studies in patients and animal models have shown that SWD are initiated in the cortex but our understanding of underlying neuronal connection alterations remain limited. We hypothesized that SWD may result from an increased neuronal connectivity. To test this hypothesis, we used a genetic model of absence-epilepsy, the GAERS rat. By studying the structural connectivity of primary somatosensory cortex, the SWD-initiating area in GAERS, by retrograde monosynaptic tracers and the functional connectivity by in vivo multi-channel extracellular electrophysiology, we were able to describe the circuit of SWD generation and propagation across cortical layers. This pathological circuit is different from the canonical circuit of sensory information processing as SWD are initiated by deep layer neurons. These neurons present an intralaminar global and a translaminar GABAergic hyperconnectivity and by decreasing these connections by synchrotron-generated microtransections we were able to reduce the power of SWD. We next investigated if the pathological circuit would interfere with sensory integration. By using a texture discrimination task we showed that sensory information integration is unaltered in GAERS. By using vibrissae stimulations during in vivo multi-channel extracellular electrophysiology recordings we showed that the canonical circuit remain functional in GAERS. Altogether, our data suggest that SWD in GAERS are generated by an abnormal structural network in the somatosensory cortex but that this pathological circuit do not interfere with the physiological function of this brain area.
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Submitted on : Monday, April 27, 2020 - 1:02:08 AM
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  • HAL Id : tel-02554916, version 1

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Florian Studer. Implication des circuits neuronaux du cortex somatosensoriel dans l’initiation de l’activité paroxystique de l’épilepsie absence. Neurobiologie. Université Grenoble Alpes, 2018. Français. ⟨NNT : 2018GREAV009⟩. ⟨tel-02554916⟩

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