Sleep stage-dependent functional coupling between PGO waves and hippocampal ensembles in mice

The sleep stage in mammals consists of rapid eye movement (REM) sleep and non-REM (NREM) sleep. Each sleep stage has its own electrophysiological characteristics. For example, REM sleep is characterized by ponto-geniculo-occipital (PGO) waves in the brainstem and theta waves in the hippocampus, and NREM sleep by sharp wave-ripples (SWRs) in the hippocampus. These are thought to be important for memory processing. To date, however, their contributions to memory have been studied independently, and no studies have addressed the relationship between hippocampal neural activities and PGO waves. PGO waves were discovered in cats in the 1950s; for more than 50 years they were thought to be absent in mice, but we have recently succeeded in recording PGO waves in mice. Here, by performing in vivo electrophysiological experiments, we unveiled the state-dependent modulatory effects of PGO waves on hippocampal excitability. During NREM sleep, hippocampal SWRs precede PGO waves. Although PGO waves are functionally coupled with SWRs, we discovered that SWRs coupled with PGO waves are short-lasting compared to SWRs without PGO waves. These results suggest that PGO waves and SWRs may contribute to memory processing in an antagonistic way. In contrast, PGO waves during REM sleep are followed by the firing of hippocampal neurons and phase-locked with hippocampal theta rhythms, suggesting that PGO waves and theta waves may make a coordinated contribution to memory processing. Therefore, we imply that PGO waves might also have a sleep state-dependent physiological role.