Abstract
Sleep involves a relative disconnection from the environment, yet sensory stimuli can still trigger awakenings. The mechanism underlying sensory vigilance and stimulus discrimination during sleep remains unclear. Here, we showed that neutral auditory stimuli evoked responses across parallel auditory and non-auditory pathways, including the auditory cortex and thalamus, the hippocampus and centro-medial thalamus (CMT). Using a convolutional neural network, we identified CMT activity as the most discriminant hub for auditory-evoked sleep-to-wake transitions among all recorded structures. Furthermore, we found that prior associative learning of auditory cues with danger (conditioned stimulus, CS+) resulted in increased awakening upon CS+ exposure during NREM, but not REM, sleep. These sleep-to-wake transitions were blocked by optogenetic silencing of CMT neurons during CS+ exposure in sleeping mice. Altogether, these results suggest a central role of the CMT neurons in the residual processing of behaviorally-relevant information in the sleeping brain functioning as one of the major hubs for awakening in response to danger.