Optogenetic activation of DRN 5-HT neurons induced active wakefulness, not quiet wakefulness

Rika Moriya, Mitsuko Kanamaru, Naoki Okuma, Akira Yoshikawa, Kenji F. Tanaka, Satoshi Hokari, Yasuyoshi Ohshima, Akihiro Yamanaka, Motoyasu Honma, Hiroshi Onimaru, Toshiaki Kikuchi, Masahiko Izumizaki

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


There has been a long-standing controversy regarding the physiological role of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) in sleep/wake architecture. Some studies have reported that 5-HT acts as a sleep-promoting agent, but several studies have suggested that DRN 5-HT neurons function predominantly to promote wakefulness and inhibit rapid eye movement (REM) sleep. Furthermore, recent studies have reported that there is a clear neurobiological difference between a waking state that includes alertness and active exploration (i.e., active wakefulness) and a waking state that is devoid of locomotion (i.e., quiet wakefulness). These states have also been shown to differ clinically in terms of memory consolidation. However, the effects of 5-HT neurons on the regulation of these two different waking states have not been fully elucidated. In the present study, we attempted to examine the physiological role of DRN 5-HT neurons in various sleep/wake states using optogenetic methods that allowed manipulation of cell-type specific neuronal activation with high temporal and anatomical precision. We crossed TPH2-tTA and TetO-ChR2(C128S) mice to obtain mice with channelrhodopsin-2 (ChR2) [C128S]-expressing central 5-HT neurons, and we activated DRN-5HT neurons or medullary 5-HT neurons. Optogenetic activation of DRN 5-HT neurons caused rapid transition from non-REM sleep to active wakefulness, not quiet wakefulness, whereas activation of medullary 5-HT neurons did not appear to affect sleep/wake states or locomotor activity. Our results may shed light on the physiological role of DRN 5-HT neurons in sleep/wake architecture and encourage further investigations of the cortical functional connectivity involved in sleep/wake state regulation.

Original languageEnglish
Pages (from-to)129-142
Number of pages14
JournalBrain Research Bulletin
Publication statusPublished - 2021 Dec


  • 5-HT neurons
  • Active wakefulness
  • Dorsal raphe nucleus
  • Optogenetics
  • Quiet wakefulness
  • Serotonin

ASJC Scopus subject areas

  • General Neuroscience


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