Caractérisation de l’activité des neurones GABAergiques immatures de CA1et de leur effet sur le réseau néonatal in-vivo
Salomé Mortet

Abstract
During the first two postnatal weeks, immature neural networks are characterized by neonatal spontaneous activities (NSA) that synchronize a large population of neurons. It is hypothesized that NSAs play an important role in the establishment of networks and their functions. In vitro, NSAs are generated within the hippocampal networks where certain types of GABAergic interneurons play a key role in network synchronization during these NSAs. In vivo, NSAs (called “early sharp waves” or eSPWs) are generated following myoclonic contractions that propagate to the hippocampus via the entorhinal cortex. However, the functional role of GABAergic activity during NSAs in vivo is still poorly understood. By combining extracellular electrophysiology with optogenetics in transgenic neonatal mice, we have characterized the involvement of GABAergic neurons during eSPWs and determined their effect on immature hippocampal networks.
We show that there is a heterogeneity of responses during eSPWs. Among the different activity patterns, we observe the presence of inhibited neurons from the first days of life. We also show that GABAergic neurons are more active than the rest of the population and participate more strongly in eSPWs. Finally, during the first week of life, optogenetic stimulation of GABAergic neurons induces inhibition in about 20% of the population. This proportion increases at the beginning of the second week of life, a period during which the excitatory effect of eSPWs decreases, reflecting the maturation of network connectivity. The late development of GABAergic inhibition would allow the network to disengage from sensory inputs induced by the periphery, enabling the emergence of the internal dynamics of the hippocampus, necessary for higher cognitive functions.

Jury
Sabine LEVI, Rapporteuse – ESPCI, Paris
Desdemona FRICKER, Rapporteuse – INCC, Paris
Alessandra PIERANI, Examinatrice – Institut Imagine, Paris
Roustem KHAZIPOV, Examinateur – Inmed, Marseille
Christophe PORCHER, Président du jury – Inmed, Marseille
Rosa COSSART, Invitée – Inmed, Marseille
Pierre-Pascal LENCK-SANTINI, Directeur de thèse – Inmed, Marseille

Thursday, March 20, 2025, 2pm, Inmed conference room