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腹侧被盖区的 GABA 神经元调节小鼠的非快速眼动睡眠。

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

机构信息

Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.

Department of Neural Regulation,Graduate School of Medicine, Nagoya University, Nagoya, Japan.

出版信息

Elife. 2019 Jun 4;8:e44928. doi: 10.7554/eLife.44928.

DOI:10.7554/eLife.44928
PMID:31159923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6548506/
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 (VTA) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTA project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTA 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. VTA showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTA directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTA terminals in the LH promoted NREM sleep. Taken together, we revealed that VTA play an important role in the regulation of NREM sleep.

摘要

睡眠/觉醒周期由睡眠和觉醒调节神经回路的协调相互作用调节。然而，其详细机制还远未被理解。在这里，我们发现腹侧被盖区 (VTA) 中的谷氨酸脱羧酶 67 阳性 GABA 能神经元是小鼠非快速眼动 (NREM) 睡眠的关键调节者。VTA 投射到多个与睡眠/觉醒调节相关的脑区，如外侧下丘脑 (LH)。VTA 的化学遗传激活促进了具有更高 δ 功率的 NREM 睡眠，而对这些 VTA 的光遗传抑制则促使其从 NREM 睡眠中迅速觉醒，即使在高度嗜睡的情况下也是如此，但不会从 REM 睡眠中觉醒。VTA 在 NREM 睡眠中表现出最高的活性，在 REM 睡眠中表现出最低的活性。此外，VTA 通过释放 GABA 直接支配并抑制促觉醒的食欲素/下丘脑分泌素神经元。因此，LH 中的 VTA 末梢的光遗传激活促进了 NREM 睡眠。综上所述，我们揭示了 VTA 在 NREM 睡眠调节中发挥着重要作用。

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