GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice
GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice
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DOI：
10.7554/elife.44928
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发表时间：
2019-06-04
期刊：
影响因子：
7.7
通讯作者：
Yamanaka, Akihiro
中科院分区：
文献类型：
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作者：
Chowdhury, Srikanta;Matsubara, Takanori;Yamanaka, Akihiro
睡眠/觉醒周期由睡眠和觉醒调节神经回路之间的协调相互作用调节。然而，详细的机制还远未被理解。在这里，我们发现腹侧被盖区（VTA（Gad 67+））的谷氨酸脱羧酶67阳性GABA能神经元是小鼠非快速眼动（NREM）睡眠的关键调节因子。VTA（Gad 67+）投射到涉及睡眠/觉醒调节的多个脑区，如外侧下丘脑（LH）。化学遗传激活VTA（Gad 67+）促进NREM睡眠具有较高的δ功率，而光遗传抑制这些诱导提示唤醒NREM睡眠，即使在高度嗜睡的条件下，但不是从REM睡眠。VTA（Gad 67+）在NREM睡眠时活性最高，REM睡眠时活性最低。此外，VTA（Gad 67+）直接支配和抑制唤醒促进食欲素/下丘脑泌素神经元释放GABA。因此，LH中VTA（Gad 67+）末端的光遗传学激活促进NREM睡眠。综上所述，我们揭示了VTA（Gad 67+）在NREM睡眠调节中起着重要作用。
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(Gad67+)) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTA(Gad67+) project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTA(Gad67+) 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(Gad67+) showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTA(Gad67+) directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTA(Gad67+) terminals in the LH promoted NREM sleep. Taken together, we revealed that VTA(Gad67+) play an important role in the regulation of NREM sleep.