Single-cell resolution functional networks during unconsciousness are segregated into spatially intermixed modules

Abstract

The common neural mechanisms underlying the reduction of consciousness during sleep and anesthesia remain unclear. Previous studies have examined changes in network structure only using recordings with limited spatial resolution, which has hindered the investigation of the critical spatial scales from the micro (single neurons) to the meso (groups of neurons) for the reduction of consciousness. To address this issue, by leveraging fast, single-cell resolution, and wide-field two-photon microscopy, we recorded calcium signals from approximately 10,000 neurons across multiple cortical regions in awake, sleeping, and anesthetized mice. This single-cell resolution data enabled us to investigate the scales at which changes in network structure compared to an awake state are commonly observed during sleep and anesthesia. We found that at the single-cell scale, both sleep and anesthesia exhibited higher network modularity, indicating a segregated network, compared to an awake state. Despite this segregation, modules were spatially intermixed in all three states. In contrast, at the mesoscale, there were no consistent differences in modularity between states, and modules were spatially localized. Our multi-scale analysis provides novel insights into the cellular-scale organization of functional networks commonly associated with the reduction of consciousness and highlights a scale-dependent organization of network structures.