Volume 32, No 2, Feb 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 2, February 2022: 139-156   |  Open Access

ORIGINAL ARTICLES

A distinct D1-MSN subpopulation down-regulates dopamine to promote negative emotional state

Zhiyuan Liu^1,† , Qiumin Le^1,† , Yanbo Lv¹ , Xi Chen¹ , Jian Cui¹ , Yiming Zhou¹ , Deqin Cheng¹ , Chaonan Ma¹ , Xiujuan Su¹ , Lei Xiao¹ , Ruyi Yang¹ , Jiayi Zhang¹ , Lan Ma^1,* , Xing Liu^1,*

¹Department of Neurosurgery, Huashan Hospital, School of Basic Medical Sciences, and Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
^†These authors contributed equally: Zhiyuan Liu, Qiumin Le
Correspondence: Lan Ma(lanma@fudan.edu.cn)Xing Liu(xingliu@fudan.edu.cn)

Dopamine (DA) level in the nucleus accumbens (NAc) is critical for reward and aversion encoding. DA released from the ventral mesencephalon (VM) DAergic neurons increases the excitability of VM-projecting D1-dopamine receptor-expressing medium spiny neurons (D1-MSNs) in the NAc to enhance DA release and augment rewards. However, how such a DA positive feedback loop is regulated to maintain DA homeostasis and reward-aversion balance remains elusive. Here we report that the ventral pallidum (VP) projection of NAc D1-MSNs (D1NAc-VP) is inhibited by rewarding stimuli and activated by aversive stimuli. In contrast to the VM projection of D1-MSN (D1NAc-VM), activation of D1NAc-VP projection induces aversion, but not reward. D1NAc-VP MSNs are distinct from the D1NAc-VM MSNs, which exhibit conventional functions of D1-MSNs. Activation of D1NAc-VP projection stimulates VM GABAergic transmission, inhibits VM DAergic neurons, and reduces DA release into the NAc. Thus, D1NAc-VP and D1NAc-VM MSNs cooperatively control NAc dopamine balance and reward-aversion states.

https://doi.org/10.1038/s41422-021-00588-5

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