GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

Srikanta Chowdhury, Takanori Matsubara, Toh Miyazaki, Daisuke Ono, Noriaki Fukatsu, Manabu Abe, Kenji Sakimura, Yuki Sudo, Akihiro Yamanaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed mechanism is far from understood. Here, we found that glutamic acid decarboxylase 67-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTAGad67+ promoted NREM sleep with higher delta power whereas optogenetic inhibition of these induced prompt arousal from NREM sleep, even under highly somnolescent conditions, but not from REM sleep. VTAGad67+ showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTAGad67+ directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTAGad67+ terminals in the LH promoted NREM sleep. Taken together, we revealed that VTAGad67+ play an important role in the regulation of NREM sleep.

Original languageEnglish
Article numbere44928
JournaleLife
Volume8
DOIs
Publication statusPublished - Jun 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Chowdhury, S., Matsubara, T., Miyazaki, T., Ono, D., Fukatsu, N., Abe, M., Sakimura, K., Sudo, Y., & Yamanaka, A. (2019). GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice. eLife, 8, [e44928]. https://doi.org/10.7554/eLife.44928