Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice

Huan Sheng; Chao Lei; Yu Yuan; Yali Fu; Dongyang Cui; Li Yang; Da Shao; Zixuan Cao; Hao Yang; Xinli Guo; Chenshan Chu; Yaxian Wen; Zhangyin Cai; Ming Chen; Bin Lai; Ping Zheng

doi:10.1038/s41467-022-35758-5

Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice

Nat Commun. 2023 Jan 5;14(1):71. doi: 10.1038/s41467-022-35758-5.

Authors

Huan Sheng^#^{1

2}, Chao Lei^#¹, Yu Yuan^#¹, Yali Fu¹, Dongyang Cui¹, Li Yang¹, Da Shao¹, Zixuan Cao¹, Hao Yang¹, Xinli Guo¹, Chenshan Chu¹, Yaxian Wen¹, Zhangyin Cai¹, Ming Chen³, Bin Lai⁴, Ping Zheng^{5

6}

Affiliations

¹ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
² Department of Otorhinolaryngology-Head and Neck Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
³ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, 200032, China. ming_chen@fudan.edu.cn.
⁴ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, 200032, China. laibin@fudan.edu.cn.
⁵ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, 200032, China. pzheng@shmu.edu.cn.
⁶ Medical College of China Three Gorges University, Yichang, 443002, China. pzheng@shmu.edu.cn.

^# Contributed equally.

Abstract

The lateral hypothalamus (LH) is physiologically critical in brain functions. The LH also plays an important role in drug addiction. However, neural circuits underlying LH involvement of drug addiction remain obscure. In the present study,our results showed that in male mice, during context-induced expression of morphine withdrawal memory, LH glutamatergic neurons played an important role; dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) projecting from the core of nucleus accumbens (NAcC) to the LH were an important upstream circuit to activate LH glutamatergic neurons; D1-MSNs projecting from the NAcC to the LH activated LH glutamatergic neurons through inhibiting LH local gamma-aminobutyric acid (GABA) neurons. These results suggest that disinhibited LH glutamatergic neurons by neural circuits from the NAcC importantly contribute to context-induced the expression of morphine withdrawal memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hypothalamic Area, Lateral / metabolism
Male
Mice
Morphine* / adverse effects
Neurons / metabolism
Nucleus Accumbens / metabolism
Receptors, Dopamine D1 / metabolism
Substance-Related Disorders* / metabolism

Substances

Morphine
Receptors, Dopamine D1