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journal article·2025-02Open access

Action Potential Firing Patterns Regulate Dopamine Release via Voltage‐Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo

Xiaoxuan Sun, Lili Yin, Zhongjun Qiao, Muhammad Younus, Guoqing Chen, Xi Wu, Jie Li, Xinjiang Kang, Huadong Xu, Li Zhou, Yinglin Li, Min Gao, Xingyu Du, Yuqi Hang, Zhaohan Lin, Liyuan Sun, Qinglong Wang, Ruiying Jiao, Lun Wang, Meiqin Hu, Yuan Wang, Rong Huang, Yiman Li, Qihui Wu, Shujiang Shang, Shu Guo, Qian Lei, Haifeng Shu, Lianghong Zheng, Shirong Wang, Feipeng Zhu, Panli Zuo, Bing Liu, Changhe Wang, Quanfeng Zhang, Zhuan Zhou

Advanced Science· Volume 12· Issue 7
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Abstract

Abstract Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown. Here by using in vivo and ex vivo models, it is shown that the AP frequency per se modulates DA release through the D2 receptor (D2R), which contributes up to 50% of total DA release. D2R has a voltage‐sensing site at D131 and can be deactivated in a frequency‐dependent manner by membrane depolarization. This voltage‐dependent D2R inhibition of DA release is mediated via the facilitation of voltage‐gated Ca2+ channels (VGCCs). Collectively, this work establishes a novel mechanism that APs per se modulate DA overflow by disinhibiting the voltage‐sensitive autoreceptor D2R and thus the facilitation of VGCCs, providing a pivotal pathway and insight into mammalian DA‐dependent functions in vivo.
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Research context

OpenAlex topics: Receptor Mechanisms and Signaling · Neural dynamics and brain function · Neuroscience and Neuropharmacology Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Membrane Biology National Biomedical Imaging Center and Institute of Molecular Medicine College of Future Technology Peking‐Tsinghua Center for Life Sciences PKU‐IDG/McGovern Institute for Brain Research Peking University Beijing 100871 China

Peking University Sixth Hospital Peking University Institute of Mental Health NHC Key Laboratory of Mental Health (Peking University) National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing 100191 China

Neuroscience Research Center Institute of Mitochondrial Biology and Medicine Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University Xi'an 710049 China

Department of Neurology the Second Affiliated Hospital of Xi'an Jiaotong University Xi'an 710004 China

Key Laboratory of Medical Electrophysiology Ministry of Education of China Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease and the Institute of Cardiovascular Research Southwest Medical University Luzhou 646000 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · National Postdoctoral Program for Innovative Talents · China Postdoctoral Science Foundation

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