Drawing the interneuronal connectivity map within the rewired epileptic hippocampus

Temporal Lobe Epilepsy (TLE) is the most prevalent type of epilepsy in adults. The disease manifests as the occurrence of unpredictable and recurrent seizures and severe disorders of mood and cognitive functions. Using mouse models, it has been pointed out several alterations of the hippocampal circuit, including a degeneration of both inhibitory and excitatory neurons, accompanied by the acquisition of aberrant intrinsic properties by survivor cells, as well as a reorganisation of the synaptic network. More particularly, inhibitory interneuron subtypes, which orchestrate the normal function of the hippocampus, are thought to play a key role to the pathological mechanisms of TLE. However, the precise input and output connectivity of hippocampal interneuron subtypes within the “re-wired” epileptic hippocampal network has not been systematically deciphered.
We propose an internship aimed at setting-up a multidisciplinary approach based on state-of the-art technologies enabling the simultaneous recording of a large population of neurons and the specific manipulation defined neuron subsets in hippocampal slices from control versus epileptic mice, particularly focusing on interneurons. More specifically, this ambitious project will allow the intern to familiarize with mouse genetic models, optogenetic and/or glutamate uncaging-based manipulation of neurons, single cell electrophysiological patch-clamp recording, network calcium imaging, and programming using Matlab. The intern will be mentored in complementary ways by Thomas MARISSAL (PhD, INSERM assistant researcher) for the biological part of the project and François MICHEL (PhD, in charge of the InMAGIC facility) for the technical component. Ultimately, we expect to draw the interneuron effective connectivity map within the epileptic hippocampus.

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