Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response

Kanako Iwasaki, Haruna Komiya, Miyo Kakizaki, Chika Miyoshi, Manabu Abe, Kenji Sakimura, Hiromasa Funato, Masashi Yanagisawa

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Sleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect of serotonin (5-HT)-deficiency on brain development and the compensation for inborn 5-HT deficiency by other sleep/wake-regulating neurons. Here, we performed selective ablation of central 5-HT neurons in the newly developed Rosa-diphtheria toxin receptor (DTR)-tdTomato mouse line that was crossed with Pet1Cre/+ mice to examine the role of 5-HT neurons in the sleep/wake behavior of adult mice. Intracerebroventricular administration of diphtheria toxin completely ablated tdTomato-positive cells in Pet1Cre/+; Rosa-DTR-tdTomato mice. Electroencephalogram/electromyogram-based sleep/wake analysis demonstrated that central 5-HT neuron ablation in adult mice decreased the time spent in rapid eye movement (REM) sleep, which was associated with fewer transitions from non-REM (NREM) sleep to REM sleep than in control mice. Central 5-HT neuron-ablated mice showed attenuated wake response to a novel environment and increased theta power during wakefulness compared to control mice. The current findings indicated that adult 5-HT neurons work to support wakefulness and regulate REM sleep time through a biased transition from NREM sleep to REM sleep.

Original languageEnglish (US)
Article number535
JournalFrontiers in Neuroscience
Issue numberAUG
StatePublished - Aug 7 2018


  • 5-HT neuron
  • Brain
  • Diphtheria toxin
  • Mouse model
  • REMS
  • Serotonin
  • Sleep

ASJC Scopus subject areas

  • Neuroscience(all)


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