Oscillatory Population-Level Activity of Dorsal Raphe Serotonergic Neurons Is Inscribed in Sleep Structure

Tomonobu Kato, Yasue Mitsukura, Keitaro Yoshida, Masaru Mimura, Norio Takata, Kenji F. Tanaka

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Dorsal raphe (DR) 5-HT neurons regulate sleep–wake transitions. Previous studies demonstrated that single-unit activity of DR 5-HT neurons is high during wakefulness, decreases during non-rapid eye movement (NREM) sleep, and ceases during rapid eye movement (REM) sleep. However, characteristics of the population-level activity of DR 5-HT neurons, which influence the entire brain, are largely unknown. Here, we measured population activities of 5-HT neurons in the male and female mouse DR across the sleep–wake cycle by ratiometric fiber photometry. We found a slow oscillatory activity of compound intracellular Ca21 signals during NREM sleep. The trough of the concave 5-HT activity increased across sleep progression, but 5-HT activity always returned to that seen during the wake period. When the trough reached a minimum and remained there, REM sleep was initiated. We also found a unique coupling of the oscillatory 5-HT activity and wideband EEG power fluctuation. Furthermore, optogenetic activation of 5-HT neurons during NREM sleep triggered a high EMG power and induced wakefulness, demonstrating a causal role of 5-HT neuron activation. Optogenetic inhibition induced REM sleep or sustained NREM, with an EEG power increase and EEG fluctuation, and pharmacological silencing of 5-HT activity using a selective serotonin reuptake inhibitor led to sustained NREM, with an EEG power decrease and EEG fluctuation. These inhibitory manipulations supported the association between oscillatory 5-HT activity and EEG fluctuation. We propose that NREM sleep is not a monotonous state, but rather it contains dynamic changes that coincide with the oscillatory population-level activity of DR 5-HT neurons.

Original languageEnglish
Pages (from-to)7244-7255
Number of pages12
JournalJournal of Neuroscience
Issue number38
Publication statusPublished - 2022 Sept 21


  • dorsal raphe
  • optogenetics
  • photometry
  • population activity
  • serotonin
  • sleep

ASJC Scopus subject areas

  • Medicine(all)


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