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Cellular Determinants of CA1 Pyramidal Cell Recruitment during Sharp-Wave Ripples

Raphael Angerbauer, Tae Ho Lim, Peter Jonas, Fritjof HelmcheniD, Xiaomin Zhang

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Abstract

Hippocampal ripples, accompanied by highly synchronous neuronal firing, are critical for immediate offline memory consolidation, learning, and planning. However, the cellular mechanisms that determine which individual neurons are recruited to participate in action potential (AP) firing during ripples remain unclear. We investigated the membrane potential (Vm) dynamics of CA1 pyramidal cells during ripples using whole-cell recordings in awake, head-fixed mice. We found that ripple participation was strongly associated with concurrent membrane-potential depolarization on an event-to-event basis, whereas between-cell differences in overall participation propensity were jointly explained by ripple-associated depolarization and intrinsic excitability. Applying this framework across CA1 cell populations revealed that differences in recruitment between superficial and deep pyramidal cells were primarily driven by ripple-associated depolarization, counteracted by excitability. Differences between place and non-place cells were similarly driven by ripple-associated depolarization, though this effect acted in the same direction as excitability. Finally, we identified the post-ripple LFP rebound as a prominent marker of ripple diversity linked to post-ripple membrane-potential hyperpolarization at the single-neuron level. Together, these findings provide a mechanistic understanding of how CA1 pyramidal cells are selectively recruited during hippocampal ripples.

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