ASTROCYTES GATE HIPPOCAMPAL SHARP-WAVE RIPPLES VIA CELL-TYPE-SPECIFIC INHIBITORY CIRCUITS

A growing body of evidence highlights the importance of distinct neuronal populations in hippocampal networks for learning and memory, and how their interactions shape circuit function. A paradigmatic example of such coordination is sharp-wave ripples (SPW-Rs), transient hippocampal network events arising from coordinated activity across nearly all neuronal cell types and essential for memory consolidation. In parallel, accumulating work points to a key role for non-neuronal cells—particularly astrocytes—in the regulation of neuronal activity across brain circuits. Yet, how astrocytes engage with distinct neuronal cell types in vivo and shape network dynamics remains poorly understood. Here, we address this gap by combining astrocyte calcium fiber-photometry with large-scale chronic electrophysiological recordings and a recently developed classifier-based framework for neuronal cell-type identification. Strikingly, we reveal a strong negative correlation between astrocytic calcium activity and SPW-R occurrence, evident already within single recording sessions and even within individual astrocytic calcium events. This negative correlation was strongest during NREM sleep, ruling out behavioural or locomotor confounds. Both CCK/Id2 and a subset of Sst interneurons remain selectively active during astrocytic calcium events, suggesting a cell-type-specific engagement of inhibitory circuits associated with reduced network excitability and astrocyte-controlled suppression of SPW-R expression. Future experiments will test the sufficiency and necessity of astrocytic control over hippocampal SPW-Rs by optogenetically activating astrocytic networks using melanopsin. Overall, our results identify a functional role for astrocytes in SPW-R dynamics, and advance our understanding of how astrocytes regulate circuit activity and memory.