Regional variation in cholinergic terminal activity determines the non-uniform occurrence of cortical slow waves during REM sleep in mice.

Sleep consists of two basic stages: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is characterized by slow high-amplitude cortical electroencephalogram (EEG) signals, while REM sleep is characterized by desynchronized cortical rhythms. Despite this, recent electrophysiological studies have suggested the presence of slow waves (SWs) in local cortical areas during REM sleep. Electrophysiological techniques, however, have been unable to resolve the regional structure of these activities because of relatively sparse sampling. Here, we map functional gradients in cortical activity during REM sleep using mesoscale imaging in mice and show local SW patterns occurring mainly in somatomotor and auditory cortical regions with minimum presence within the default mode network. The role of the cholinergic system in local desynchronization during REM sleep is also explored by calcium imaging of cholinergic activity within the cortex and analyzing structural data. We demonstrate weaker cholinergic projections and terminal activity in regions exhibiting frequent SWs during REM sleep.

Formation and reverberation of sequential neural activity patterns evoked by sensory stimulation are enhanced during cortical desynchronization.

Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.