Phase-specific pooling of sparse assembly activity by respiration-related brain oscillations

Nasal breathing affects cognitive functions, but it has remained largely unclear how respiration-driven inputs shape information processing in neuronal circuits. Current theories emphasize the role of neuronal assemblies, coalitions of transiently active pyramidal cells, as the core unit of cortical network computations. Here, we show that the phase of respiration-related oscillations (RROs) influences the likelihood of activation of a subset of neuronal assemblies in the medial prefrontal cortex of awake mice. RROs bias the activation of neuronal assemblies more efficiently than that of individual neurons by entraining the coactivity of assembly neurons. Moreover, the activation of assemblies is moderately biased towards the descending phase of RROs. Despite the enriched activation of assemblies during descending RRO, the overlap between individual assemblies remains constant across RRO phases. Putative GABAergic interneurons are shown to coactivate with assemblies and receive enhanced excitatory drive from assembly neurons during descending RRO, suggesting that the phase-specific recruitment of putative interneurons might help to keep the activation of different assemblies separated from each other during times of preferred assembly activation. Our results thus identify respiration-synchronized brain rhythms as drivers of neuronal assemblies and point to a role of RROs in defining time windows of enhanced yet segregated assembly activity. KEY POINTS: Activation of neuronal assemblies is phase-coupled to ongoing respiration-related oscillations (RROs) in the medial prefrontal cortex of mice. The phase coupling strength of assemblies exceeds that of individual neurons. Assemblies preferentially activate during the descending phase of RRO. Despite higher assembly frequency during descending RRO, overlap between active assemblies remains constant across RRO phase. Putative GABAergic interneurons are preferentially recruited by assembly neurons during descending RRO, suggesting that interneurons might contribute to the segregation of active assemblies during the descending phase of RRO.