The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep–wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep–wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

嘴内侧被盖核（RMTg），也称为腹侧被盖区的 GABA 能尾，投射到中脑多巴胺能系统、中缝背核、蓝斑和其他区域。 RMTg 是否参与睡眠-觉醒调节尚不清楚。在本研究中，大鼠 RMTg 神经元的药物遗传学激活促进非快速眼动 (NREM) 睡眠，并增加慢波活动 (SWA)。相反，神经毒性损伤 8 或 16 天后的大鼠表现出 NREM 睡眠减少，开灯时 SWA 减少。损伤后 SWA 的减少持续至少 25 天。同样，大鼠 RMTg 神经元的药理学和药物遗传学失活会减少 NREM 睡眠。电生理学实验与光遗传学相结合表明，RMTg 神经元末端与中脑多巴胺能神经元之间存在直接抑制连接。 RMTg 对睡眠-觉醒周期的双向影响是通过使用药物遗传学方法调节腹侧被盖区 (VTA)/黑质致密区 (SNc) 多巴胺能神经元活动来模拟的。此外，在 6 小时睡眠剥夺后的 2 小时恢复期内，与基线水平相比，病变大鼠和对照大鼠的 NREM 睡眠时间均显着增加；然而，与基线水平相比，只有对照大鼠的 SWA 显着增加。总的来说，我们的研究结果揭示了 RMTg 在促进 NREM 睡眠和稳态调节中的重要作用。