近期论文

Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors.(IF=12.353)

 2018 Apr 20;9(1):1576. doi: 10.1038/s41467-018-03889-3.

Luo YJ1,2,3,4Li YD1Wang L1,2,3Yang SR1,2,3Yuan XS1Wang J1Cherasse Y5Lazarus M5Chen JF6Qu WM7,8,9Huang ZL10,11,12.

Author information

1.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.
2.Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences,, Fudan University, Shanghai, 200032, China.
3.Shanghai Key Laboratory of Clinical Geriatric Medicine,, Fudan University, Shanghai, 200032, China.
4.Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 201108, China.
5.International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
6.The Institute of Molecular Medicine, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
7.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. quweimin@fudan.edu.cn.
8.Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences,, Fudan University, Shanghai, 200032, China. quweimin@fudan.edu.cn.
9.Shanghai Key Laboratory of Clinical Geriatric Medicine,, Fudan University, Shanghai, 200032, China. quweimin@fudan.edu.cn.
10.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. huangzl@fudan.edu.cn.
11.Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences,, Fudan University, Shanghai, 200032, China. huangzl@fudan.edu.cn.
12.Shanghai Key Laboratory of Clinical Geriatric Medicine,, Fudan University, Shanghai, 200032, China. huangzl@fudan.edu.cn.
 

Abstract

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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