Department of Pharmacology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences; Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences,, Fudan University, Shanghai, 200032, China.
Nat Commun. 2018 Apr 20;9(1):1576. doi: 10.1038/s41467-018-03889-3.
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear. Here, we demonstrate that NAc dopamine D receptor (DR)-expressing neurons are essential for behavioral arousal. Using in vivo fiber photometry in mice, we find arousal-dependent increases in population activity of NAc DR neurons. Optogenetic activation of NAc DR neurons induces immediate transitions from non-rapid eye movement sleep to wakefulness, and chemogenetic stimulation prolongs arousal, with decreased food intake. Patch-clamp, tracing, immunohistochemistry, and electron microscopy reveal that NAc DR neurons project to the midbrain and lateral hypothalamus, and might disinhibit midbrain dopamine neurons and lateral hypothalamus orexin neurons. Photoactivation of terminals in the midbrain and lateral hypothalamus is sufficient to induce wakefulness. Silencing of NAc DR neurons suppresses arousal, with increased nest-building behaviors. Collectively, our data indicate that NAc DR neuron circuits are essential for the induction and maintenance of wakefulness.
伏隔核（NAc）参与依赖于觉醒增加的行为，但它对觉醒的影响尚不清楚。在这里，我们证明 NAc 多巴胺 D 受体（DR）表达神经元对于行为觉醒是必不可少的。我们使用小鼠体内光纤光度测定法发现，NAc DR 神经元的群体活动随着觉醒而增加。光遗传学激活 NAc DR 神经元会立即促使非快速眼动睡眠向觉醒状态转变，而化学遗传刺激则延长觉醒时间，同时减少食物摄入。膜片钳、示踪、免疫组织化学和电子显微镜显示，NAc DR 神经元投射到中脑和外侧下丘脑，可能抑制中脑多巴胺神经元和外侧下丘脑食欲素神经元。中脑和外侧下丘脑的末梢光激活足以诱导觉醒。NAc DR 神经元的沉默抑制觉醒，同时增加筑巢行为。总的来说，我们的数据表明，NAc DR 神经元回路对于诱导和维持觉醒是必不可少的。
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