Neuronal ensembles in visual cortex reactivate during hypnagogic sleep onset

During sleep onset (i.e. hypnagogia), visual hallucinations can occur in healthy human subjects following prolonged sensory experience. These percepts at sleep onset also occur in amnesiac patients and have signatures in human scalp electroencephalography recordings, suggesting a cortical origin. At the cellular level, neuronal ensembles, defined as groups of coactive neurons, dominate cortical activity and are causally related to perceptual states and behavior. To better understand the circuit mechanisms underlying hypnagogic visual hallucinations during sleep onset, we imaged neuronal activity in the rodent visual cortex during wake and sleep brain states following the repeated presentation of visual stimuli. We find that NREM1 sleep is the primary brain state at sleep onset, and neuronal ensemble properties during sleep are similar to wake. Interestingly, following prolonged visual stimulation, neuronal ensembles in visual cortex recruited by visual stimuli or locomotion had increased activity specifically during NREM1 sleep, consistent with the presence of hypnagogic hallucinations. Moreover, neuronal ensembles defined during visual stimulus periods were already present in visual cortex preceding visual stimulation. We propose that neuronal ensembles form an endogenous lexicon of cortical activity that are specifically recruited by sensory stimuli, and that specific neuronal ensembles become reactivated in visual cortex during hypnagogic sleep onset following prolonged sensory experience.