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bioRxiv · 10.1101/2025.06.17.660075

Parallel emergence of perisomatic inhibition and ripples in the developing hippocampal circuit

Da Silva, A. F. G.·Dubanet, O.·Rouault, H.·Leinekugel, X.
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Abstract

During hippocampal Sharp Wave Ripples, sequences of awake coding activities are replayed with a rhythmic timing and high level of synchrony favorable for synaptic plasticity and transfer of information to downstream structures. Previous work reported the emergence of ripples at P10 in the CA1 region, together with the development of inhibition. On the other hand, neither the relationships between perisomatic inhibition and ripples nor their developmental emergence have been investigated in CA3, in which ripples have a different frequency profile (90-110Hz instead of 140-200Hz in CA1), functional perisomatic inhibitory circuits have different properties, and some developmental aspects such as neurogenesis or interneuron maturation are early compared to CA1. We have here investigated the hypothesis of a conjoint and earlier appearance and maturation of ripples and perisomatic inhibition in the CA3 hippocampal region compared to CA1. We report a parallel sequence of events in CA3 and CA1, starting with the early expression of perisomatic GABAergic synaptic activity combined with the emergence of ripple activity. Interestingly, perisomatic inhibition and ripple activity follow parallel maturation trajectories, beginning in CA3 at P7 with immature (i.e. not functional yet) inhibition and immature ripples (proto-ripples) with labile oscillatory frequency. Mature functional perisomatic inhibition and clear high-frequency ripple activity progressively emerge between P10 and P12, reaching adult-like properties by P13. A similarly progressive maturation of ripples occurs in CA1, from P11 to P15. The progressive emergence of functional inhibition and specific patterns of neuronal activity likely support the progressive emergence of cognitive function to which they are necessary prerequisite.

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Da Silva, A. F. G., Dubanet, O., Rouault, H., Leinekugel, X.. 2025-06-21. Parallel emergence of perisomatic inhibition and ripples in the developing hippocampal circuit. https://doi.org/10.1101/2025.06.17.660075

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