Kevin N Schneider, Minke H C Nota, Hallie Lazaro, Daniel R Rijsketic, Michelle Jin, Carlie Neiswanger, Asad Beck, Nick Ressler, Jason J Q Zhang, Amelia Li, Cole C Shin, Ella Apley, Glorianna I Gutierrez, Ainsley C Barrow, Ian Campuzano, Alexandria D Murry, Jovana Navarrete, Eric R Szelenyi, Kentaro K Ishii, Simon R O Nilsson, Garret D Stuber, Christine A Denny, Michael R Bruchas, Boris D Heifets, Horacio O de la Iglesia, Sam A Gloden, Mitra Heshmati
UNLABELLED: 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.
HIGHLIGHTS: A distributed brain-wide ensemble comprises anesthesia unconsciousnessLateral parabrachial nucleus is a key, preferentially activated hubBrain-wide or parabrachial ensemble re-activation induces altered consciousness.