Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation

Tomomi Tsunematsu, Takafumi Ueno, Sawako Tabuchi, Ayumu Inutsuka, Kenji Tanaka, Hidetoshi Hasuwa, Thomas S. Kilduff, Akira Terao, Akihiro Yamanaka

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep.

Original languageEnglish
Pages (from-to)6896-6909
Number of pages14
JournalJournal of Neuroscience
Volume34
Issue number20
DOIs
Publication statusPublished - 2014

Fingerprint

Optogenetics
Sleep
Neurons
REM Sleep
Wakefulness
melanin-concentrating hormone
Lateral Hypothalamic Area
Diphtheria Toxin
Eye Movements
Tetracycline
Neuropeptides
Transgenic Mice

Keywords

  • Ablation
  • Cell fate
  • Channelrhodopsin2
  • Hypothalamus
  • Optogenetics
  • REM sleep

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. / Tsunematsu, Tomomi; Ueno, Takafumi; Tabuchi, Sawako; Inutsuka, Ayumu; Tanaka, Kenji; Hasuwa, Hidetoshi; Kilduff, Thomas S.; Terao, Akira; Yamanaka, Akihiro.

In: Journal of Neuroscience, Vol. 34, No. 20, 2014, p. 6896-6909.

Research output: Contribution to journalArticle

Tsunematsu, Tomomi ; Ueno, Takafumi ; Tabuchi, Sawako ; Inutsuka, Ayumu ; Tanaka, Kenji ; Hasuwa, Hidetoshi ; Kilduff, Thomas S. ; Terao, Akira ; Yamanaka, Akihiro. / Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 20. pp. 6896-6909.
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