Mécanismes synaptiques et de réseau des ondes aiguës précoces dans l’hippocampe du rongeur en période néonatale
Azat GAINUTDINOV – Team “Early activity in the developing brain”

Abstract
In the neonatal rodent hippocampus, early sharp waves (eSPWs) represent the first organized activity pattern, emerging as transient, recurrent bursts of neuronal network activity. This thesis investigates the mechanisms underlying eSPW generation, and their synaptic correlates in context of developmental maturation of hippocampal inhibition.
The study begins by exploring the role of somatosensory stimulation in evoking eSPWs. Experiments demonstrated that electrical stimulation of whisker pads and limbs reliably induces eSPWs, showing temporal and spatial characteristics similar to spontaneous events. The current-source density (CSD) profiles revealed the involvement of temporoammonic and perforant pathways, linking external sensory inputs to hippocampal activity.
The temporal dynamics of synaptic responses during eSPWs in vivo and during responses evoked by stimulation of the temporo-ammonic and perforant pathways in the in vitro preparations were analysed using patch-clamp recordings in the CA1 and DG regions. Analysis revealed that excitatory postsynaptic currents (EPSCs) precede inhibitory postsynaptic currents (IPSCs) by tens of milliseconds, creating a broad integration window for excitatory input. This delay narrows as inhibition matures, aligning with the developmental progression of feedforward inhibition (FFI).
Finally, immunohistochemical analysis mapped the distribution and developmental placement of future parvalbumin inhibitory synapses in the CA1 region of the hippocampus. The results of this analysis suggest that dendritic synapses made by parvalbumin interneurons form earlier than perisomatic synapses.
Taken together, these results indicate a key role for external excitatory inputs in the activation of the immature hippocampal neuronal network and also suggest a delayed development of inhibition in the hippocampus, which together create conditions for bursting activity in the hippocampus during early development
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Jury
Dirk ISBRANDT, Rapporteur DZNE – Allemagne, Cologne
Anton SIROTA, Rapporteur LMU – Allemagne, Munich
Matthew COLONNESE, Examinateur GWU – États-Unis, Washington, D.C.
Christophe PORCHER ,Président du jury INMED – Marseille
Roustem KHAZIPOV, Directeur de thèse INMED – Marseille
Agnès BAUDE, Co-directrice de thèse INMED – Marseille

Tuesday, March 18th at 2:00pm – INMED conference room