Genetic capture for conscious state transitions

Spatially integrated mechanisms of consciousness are unclear. An approach to manipulate brainwide circuits regulating consciousness via synthetic central nervous system activation may pave the way for more precise transitions in consciousness and reveal underlying mechanisms. Toward this goal, we leverage anesthesia as a tool to probe consciousness at cellular resolution within the intact network. We perform brainwide chemogenetic capture of isoflurane anesthesia-activated circuitry in mice —in parallel with electrocorticography, wireless mechano-acoustic recording of peripheral physiology, and behavioral classification— to describe a synthetic state of altered consciousness generated in the absence of an anesthetic agent. We define patterns of activation under isoflurane using intact brain immediate early gene mapping combined with brainwide high density silicon probe recordings. Our data identify subcortical hotspots of neural activity in an unconsciousness network that is globally characterized by increased functional connectivity driven by select nodes. We provide technical resources spanning brainwide single-cell resolution maps and neurophysiologic datasets of the isoflurane-rendered unconscious state, along with an approach to further probe its global cellular-level mechanisms. Together, we present the foundation for future research to refine this viral-genetic brainwide approach to generate synthetic conscious state transitions, such as sleep, stasis, analgesia or anesthesia.