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A microcircuit model for initiation and reward-dependent termination of hippocampal replay

Musset, H.; Fukai, T.

2026-01-19 neuroscience
10.64898/2026.01.18.700234 bioRxiv
Show abstract

Sharp-wave ripples (SWRs) serve as a key network state in which the hippocampus replays spatiotemporal patterns that reflect animals experiences. However, how the hippocampal circuitry controls the generation, duration, and termination of these events remains unclear. To clarify how behaviorally salient locations are encoded into replay, we constructed a biologically plausible model of area CA3, including three classes of inhibitory neurons -- parvalbumin-positive basket cells, cholecystokinin-positive basket cells (CCKBC), and theta-OFF, ripple-ON cells (TORO). In our model, replay and SWRs emerge from TORO-mediated release of CCKBC inhibition onto pyramidal cells, as hypothesized by experiments. Furthermore, our model suggests that short-term depression at TORO-CCKBC synapses controls replay duration and identifies a mechanism through which replay overrepresents reward-associated locations. Our model predicts that replays terminating at these locations are shorter, which we confirm in experimental data. Overall, this study provides a mechanistic framework for SWRs and replay dynamics in the hippocampus.

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