Neuronal ensembles in visual cortex reactivate during hypnagogic sleep onset

Abstract

Abstract 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. One-Sentence Summary Prolonged sensory experience induces the activity of endogenous neuronal ensembles in rodent visual cortex during sleep onset, providing a circuit mechanism for the hypnagogic hallucinations reported in human subjects. Summary The encoding of perceptual memory is believed to rely on the coactivity of ensembles of neurons. Hypnagogic images during sleep onset have been reported in healthy human subjects following extended visual stimulus presentation. To investigate this phenomenon at the cellular scale, we monitored populations of neurons in mouse visual cortex with two-photon imaging across wake and sleep states following repeated visual stimulus presentation. We found that visually recruited neuronal ensembles had increased activity during brain states of sleep onset, matching human findings. Analyzing neuronal activity prior to visual stimulus presentation uncovered visually recruited ensembles were already present during wake and sleep states. We propose that hypnagogic images are encoded on a pre-configured lexicon of ensembles in the visual cortex.