Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D(1) receptors.

Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D(1) receptors.
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伏隔核通过表达多巴胺 D1 受体的神经元亚群控制觉醒

DOI:
10.1038/s41467-018-03889-3
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发表时间:
2018-04-20
影响因子:
16.6
通讯作者:
Huang ZL
Huang ZL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Luo YJ;Li YD;Wang L;Yang SR;Yuan XS;Wang J;Cherasse Y;Lazarus M;Chen JF;Qu WM;Huang ZL

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延髓核(NAc)参与依赖于高度觉醒的行为,但其对唤醒的影响仍不清楚。在这里,我们证明了NAc多巴胺D1受体(D1 R)表达神经元是必不可少的行为唤醒。在小鼠体内使用纤维光度法,我们发现觉醒依赖的NAc D1 R神经元的群体活动增加。NAc D1 R神经元的光遗传学激活诱导从非快速眼动睡眠到觉醒的立即转变,以及化学遗传学刺激-觉醒,伴随食物摄入减少。膜片钳、示踪、免疫组织化学和电镜观察显示,NAc D1 R神经元投射到中脑和外侧下丘脑,并可能解除中脑多巴胺神经元和外侧下丘脑食欲素神经元的抑制。中脑和外侧下丘脑的光激活足以引起觉醒。NAc D1 R神经元的沉默抑制觉醒,增加筑巢行为。总的来说,我们的数据表明,NAc D1 R神经元电路的诱导和维持清醒是必不可少的。
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 D1 receptor (D1R)-expressing neurons are essential for behavioral arousal. Using in vivo fiber photometry in mice, we find arousal-dependent increases in population activity of NAc D1R neurons. Optogenetic activation of NAc D1R 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 D1R 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 D1R neurons suppresses arousal, with increased nest-building behaviors. Collectively, our data indicate that NAc D1R neuron circuits are essential for the induction and maintenance of wakefulness.
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期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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