Local inhibitory topology dictates the spatial compartmentalization of hippocampal sharp-wave ripples

Abstract

Hippocampal sharp-wave ripples (SWRs) are essential for memory consolidation and represent among the most synchronous oscillatory events in the brain. Yet, despite their capacity for widespread synchronization, SWRs frequently remain confined to discrete hippocampal domains, revealing a paradox between global coordination and local autonomy. Here, by analysing existing in vivo recordings with an experimentally constrained three-dimensional biophysical model, we show that inhibitory activity and inhibitory topology serve fundamentally distinct functions. Whereas perisomatic inhibition gates SWR generation and dendritic inhibition regulates the strength and spectral properties of ripple oscillations, the spatial organization of inhibitory connectivity establishes local computational domains that enable autonomous ripple generators to coexist. Together, our findings identify a spatial dimension of inhibition, in which inhibitory activity governs the emergence and dynamics of SWRs, while inhibitory topology determines their spatial organization and autonomy.