NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice

Cell Rep. 2024 Mar 5;43(3):113905. doi: 10.1016/j.celrep.2024.113905.

Jie Huang ¹, Yan-Yan Zhang ², Yu-Yang Qiu ², Shan Yao ², Wan-Ting Qiu ², Jin-Lin Peng ³, Yuan-Quan Li ⁴, Qiang-Long You ², Cui-Hong Wu ², Er-Jian Wu ², Jin Wang ⁵, Yan-Ling Zhou ⁶, Yu-Ping Ning ⁶, Hong-Sheng Wang ⁷, Wen-Bing Chen ², Bing-Jie Hu ⁸, Youtan Liu ⁹, Xiang-Dong Sun ¹⁰

Affiliations

1 Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
2 Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, and Emergency Department of the Second Affiliated Hospital, School of Basic Medicine, Guangzhou Medical University, Guangzhou, China.
3 Guangzhou Medical University-Guangzhou Institute of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
4 Department of Neurology, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
5 Department of Physiology, Guangxi University of Science and Technology, Liuzhou, China.
6 Department of Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
7 Songjiang Research Institute, Shanghai Songjiang District Central Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
8 Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, and Emergency Department of the Second Affiliated Hospital, School of Basic Medicine, Guangzhou Medical University, Guangzhou, China. Electronic address: [email protected].
9 Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China. Electronic address: [email protected].
10 Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address: [email protected].

PMID: 38446660 DOI: 10.1016/j.celrep.2024.113905

Abstract

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Keywords

CP: Neuroscience; ErbB4; NRG1; mating motivation; medial amygdala.

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