Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors

Yan-Jia Luo, Ya-Dong Li, Lu Wang, Su-Rong Yang, Xiang-Shan Yuan, Juan Wang, Yoan Cherasse, Michael Lazarus, Jiang-Fan Chen, Wei-Min Qu () and Zhi-Li Huang ()
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Yan-Jia Luo: Fudan University
Ya-Dong Li: Fudan University
Lu Wang: Fudan University
Su-Rong Yang: Fudan University
Xiang-Shan Yuan: Fudan University
Juan Wang: Fudan University
Yoan Cherasse: University of Tsukuba
Michael Lazarus: University of Tsukuba
Jiang-Fan Chen: Wenzhou Medical University
Wei-Min Qu: Fudan University
Zhi-Li Huang: Fudan University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03889-3

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