Pathophysiological study of temporal lobe epilepsy: detailed analysis of parvalbumin interneuron myelination and glial reactions
Team “Neuronal coding and plasticity in epilepsy”

Abstract
The pathophysiological mechanisms of temporal lobe epilepsy (TLE), one of the most common forms of epilepsy, include a major reorganization of neuronal networks, particularly inhibitory circuits. However, it has recently been shown that the axons of parvalbumin (PV) interneurons in the hippocampus are myelinated under non-epileptic conditions, which plays an essential role in physiological activity. Studies on TLE have reported alterations in hippocampal myelination, accompanied by a strong glial and inflammatory response. In contrast, interneuron myelination has not been specifically studied under epileptic conditions.
I hypothesize that myelination of CA1 PV interneurons is impaired in TLE. I studied the myelination of these interneurons at different stages (early and chronic) of TLE in a chronic epileptic mouse model. In addition, I analyzed the density of oligodendrocytes and their progenitors involved in myelination, as well as the microglial response.
My results show impairment of the myelination pattern of CA1 PV interneurons during epileptogenesis, with a strong microglial and oligodendrocyte response. Blocking the microglial reaction with GW2580 partially restores the myelination patterns of PV interneurons and blocks the oligodendrocyte reaction. This study, which reveals impaired myelination of PV interneurons associated with a microglial reaction, provides a new perspective in understanding the early pathological mechanisms of TLE.

Jury
Desdemona Fricker, Rapportrice – Integrative Neuroscience & Cognition Center (INCC), Paris
Etienne Audinat, Rapporteur – Institute of Functional Genomics (IGF), Montpellier,
Christophe Porcher, Examinateur & Président du jury – Institut de Neurobiologie de la Méditerranée (INMED), Marseille
Valérie Crépel, Directrice de thèse – Institut de Neurobiologie de la Méditerranée (INMED), Marseille

Thursday 7 December 2023 at 2pm – Inmed conference room