Unravel the Neuronal Pathways Underlying Anesthesia-Induced Loss of Consciousness
General anesthesia is a reversible, drug-induced brain state comprised of unconsciousness, amnesia, analgesia and immobility with stability and control of vital physiological systems. Yet the mechanism by which anesthetic drugs induce such brain state remains largely a mystery in neuroscience and medicine. We are particularly interested in unraveling the neural pathways and systems through which anesthetics induce the reversible loss of consciousness (LOC). To this end, we are able to use an innovative technology to specifically label neurons in the brain that areactivated under general anesthesia, and we discovered that such neurons are all GABAergic inhibitory neurons. Notably, there is a group of anesthesia-activated neurons locates in hypothalamic regions overlapping with those previously implicated in sleep. Since NREM (non-rapid eye movement) sleep is a physiological unconscious state, this preliminary finding suggests that these neurons may represent a key system that induces or maintains the LOC state in both sleep and general anesthesia. In this proposal, we will address three critical questions: what are the output targets of the anesthetics-activated hypothalamic neurons, what are the in vivo activities of these neurons in sleep, awake, anesthetized states and during transitions between these states, and finally what are the causal functions of these neurons? This study is expected to begin to unveil the precise neural pathways that suppress consciousness, with a potential to reveal a critical therapeutic target for restoring consciousness in patients in coma and vegetative state.