Breathing modulates cortico-hippocampal dynamics during offline states

Abstract Network dynamics have been proposed as a mechanistic substrate for the information transfer across cortical and hippocampal circuits. During sleep and offline states, synchronous reactivation across these regions underlies the consolidation of memories. However, little is known about the mechanisms that synchronize and coordinate these processes across widespread brain regions. Here we address the hypothesis that breathing acts as an oscillatory pacemaker, persistently coupling distributed brain circuit dynamics. Using large-scale recordings from seven cortical and subcortical brain regions in quiescent and sleeping mice, we identified a novel global mechanism, termed respiratory corollary discharge, that co-modulates neural activity across these circuits. Analysis of inter-regional population activity and optogenetic perturbations revealed that breathing rhythm couples hippocampal sharp-wave ripples and cortical DOWN/UP state transitions by jointly modulating excitability in these circuits. These results highlight breathing, a perennial brain rhythm, as an oscillatory scaffold for the functional coordination of the limbic circuit, supporting the segregation and integration of information flow across neuronal networks during offline states.