Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble

Abstract

Neural circuits underlying unconsciousness remain poorly defined. We test the hypothesis that unconsciousness arises from specific, distributed circuits using general anesthesia in mice as a reproducible model. We identify a cortical-to-subcortical shift in neural activity during isoflurane anesthesia that is organized into nine discrete functional communities mapped at single-cell resolution. The lateral parabrachial nucleus (LPB) emerges as a central hub, exhibiting high interconnectivity, spontaneous firing under anesthesia, and preferential recruitment during reactivation of the brain-wide ensemble confirmed by single unit recordings. Chemogenetic reactivation of the captured brain-wide ensemble induces sedation, slow wave oscillations, hypothermia, and analgesia, which are components of anesthesia-induced unconsciousness. Reactivation of the LPB ensemble alone recapitulates a subset of these effects. Together, we define a global neural substrate for unconsciousness and recapitulate its dissociable autonomic, neurophysiologic, and behavioral effects using brain-wide ensemble manipulations. These results establish a neural circuit framework for anesthesia-induced unconsciousness in the mammalian brain.