Sleep and Wakefulness Are Controlled by Ventral Medial Midbrain/Pons GABAergic Neurons in Mice
Sleep and Wakefulness Are Controlled by Ventral Medial Midbrain/Pons GABAergic Neurons in Mice
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DOI：
10.1523/jneurosci.0598-18.2018
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发表时间：
2018-11-21
影响因子：
5.3
通讯作者：
Lazarus, Michael
中科院分区：
文献类型：
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作者：
Takata, Yohko;Oishi, Yo;Lazarus, Michael
睡眠-觉醒行为是由哺乳动物大脑中广泛的神经元群体控制的。虽然腹侧中脑/脑桥（VMP）区被认为参与了睡眠-觉醒调节，但其神经元机制仍不清楚。在这里，我们发现，非特异性细胞消融或选择性消融GABA能神经元表达白喉毒素片段A的VMP在雄性小鼠诱导觉醒，持续至少4周的大幅增加。相比之下，选择性消融VMP中的多巴胺能神经元对觉醒几乎没有影响。VMP GABA能神经元的化学发生抑制也显著增加觉醒。给予多巴胺D1或D2/3受体拮抗剂可不同程度地减弱或抑制VMP GABA能神经元消融或抑制的促醒作用，同时给予两种拮抗剂可消除促醒作用。相反，VMP GABA能神经元的化学激活非常强烈地增加慢波睡眠和减少觉醒。这些结果表明，VMP GABA能神经元调节小鼠睡眠-觉醒行为中的多巴胺能活动。
Sleep-wake behavior is controlled by a wide range of neuronal populations in the mammalian brain. Although the ventral midbrain/pons (VMP) area is suggested to participate in sleep-wake regulation, the neuronal mechanisms have remained unclear. Here, we found that nonspecific cell ablation or selective ablation of GABAergic neurons by expressing diphtheria toxin fragment A in the VMP in male mice induced a large increase in wakefulness that lasted at least 4 weeks. In contrast, selective ablation of dopaminergic neurons in the VMP had little effect on wakefulness. Chemogenetic inhibition of VMP GABAergic neurons also markedly increased wakefulness. The wake-promoting effect of the VMP GABAergic neuron ablation or inhibition was attenuated to varying degrees by the administration of dopamine D1 or D2/3 receptor antagonists and abolished by the administration of both antagonists together. In contrast, chemogenetic activation of VMP GABAergic neurons very strongly increased slow-wave sleep and reduced wakefulness. These findings suggest that VMP GABAergic neurons regulate dopaminergic actions in the sleep-wake behavior of mice.