Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D2R-mediated Sleep Reduction
Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D2R-mediated Sleep Reduction
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DOI：
10.1016/j.isci.2020.101240
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发表时间：
2020-06-26
期刊：
影响因子：
5.8
通讯作者：
Oishi, Yo
中科院分区：
文献类型：
--
作者：
Honda, Takato;Takata, Yohko;Oishi, Yo
患有神经精神障碍躁狂症的人表现出多动症、情绪高涨和睡眠需求减少。然而，参与躁狂样行为的脑区和神经元群体尚未被阐明。在本研究中，我们发现，消融腹侧中脑/桥脑(VMP)GABA能神经元诱导小鼠的躁狂样行为，包括多动、抗抑郁行为、减少焦虑、增加冒险行为、注意力分散和极短的睡眠时间。值得注意的是，在睡眠剥夺后，这些米歇尔·苏没有表现出反弹的睡眠，这表明睡眠稳态调节异常。多巴胺D-2受体缺陷在很大程度上消除了VMP GABA能神经元消融所引起的睡眠减少，而不影响其多动和抗抑郁行为。我们的研究结果表明，VMP GABA能神经元参与躁狂样行为的表达，根据多巴胺D-2受体可将躁狂样行为分为短睡型和其他表型。
Individuals with the neuropsychiatric disorder mania exhibit hyperactivity,elevated mood, and a decreased need for sleep. The brain areas and neuronal populations involved in mania-like behaviors, however, have not been elucidated.In this study, we found that ablating the ventral medial midbrain/pons (VMP) GABAergic neurons induced mania-like behaviors in mice, including hyperactivity, anti-depressive behaviors, reduced anxiety, increased risk-taking behaviors, distractibility, and an extremely shortened sleep time. Strikingly, these miceal so showed no rebound sleep after sleep deprivation, suggesting abnormal sleep homeostatic regulation. Dopamine D-2 receptor deficiency largely abolished the sleep reduction induced by ablating the VMP GABAergic neurons without affecting the hyperactivity and anti-depressive behaviors. Our data demonstrate that VMP GABAergic neurons are involved in the expression of mania-like behaviors,which can be segregated to the short-sleep and other phenotypes on the basis of the dopamine D-2 receptors.