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

eLife | 2019

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.

Pubmed ID: 31159923 RIS Download

Associated grants

  • Agency: Japan Science and Technology Agency, International
    Id: JPMJCR1656
  • Agency: Ministry of Education, Culture, Sports, Science, and Technology, International
    Id: 17H05563
  • Agency: Ministry of Education, Culture, Sports, Science and Technology, International
    Id: 18KK0223
  • Agency: Ministry of Education, Culture, Sports, Science and Technology, International
    Id: 18H05124
  • Agency: Ministry of Education, Culture, Sports, Science and Technology, International
    Id: 16H01271
  • Agency: Ministry of Education, Culture, Sports, Science and Technology, International
    Id: 18H02523
  • Agency: Ministry of Education, Culture, Sports, Science and Technology, International
    Id: 19H05016

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