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 journalArticle

Abstract

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.

LanguageEnglish (US)
Article number535
JournalFrontiers in Neuroscience
Volume12
Issue numberAUG
DOIs
StatePublished - Aug 7 2018

Fingerprint

Serotonergic Neurons
REM Sleep
Arousal
Sleep
Serotonin
Neurons
Wakefulness
Diphtheria Toxin
Adrenergic Neurons
Electromyography
Eye Movements
Electroencephalography

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response. / Iwasaki, Kanako; Komiya, Haruna; Kakizaki, Miyo; Miyoshi, Chika; Abe, Manabu; Sakimura, Kenji; Funato, Hiromasa; Yanagisawa, Masashi.

In: Frontiers in Neuroscience, Vol. 12, No. AUG, 535, 07.08.2018.

Research output: Contribution to journalArticle

Iwasaki, Kanako ; Komiya, Haruna ; Kakizaki, Miyo ; Miyoshi, Chika ; Abe, Manabu ; Sakimura, Kenji ; Funato, Hiromasa ; Yanagisawa, Masashi. / Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response. In: Frontiers in Neuroscience. 2018 ; Vol. 12, No. AUG.
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