Action Potential Firing Patterns Regulate Dopamine Release via Voltage‐Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo
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 Ca<sup>2+</sup> 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.
Authors
- Xiaoxuan Sun (ORCID: https://orcid.org/0000-0002-4909-1295)
- Yiman Li (ORCID: https://orcid.org/0000-0003-0595-3401)
- Hua‐Dong Xu (ORCID: https://orcid.org/0000-0002-4510-3754)
- Zhuan Zhou (ORCID: https://orcid.org/0000-0001-9048-6638)
- Xinjiang Kang (ORCID: https://orcid.org/0000-0003-0877-2438)
- Xingyu Du
- Rong Huang (ORCID: https://orcid.org/0000-0002-6901-5089)
- Feipeng Zhu (ORCID: https://orcid.org/0000-0002-3096-8309)
- Liyuan Sun
- Changhe Wang (ORCID: https://orcid.org/0000-0002-5902-2277)
- Lili Yin (ORCID: https://orcid.org/0000-0002-3649-1994)
- Ruiying Jiao
- Lun Wang (ORCID: https://orcid.org/0000-0002-6505-9674)
- Meiqin Hu (ORCID: https://orcid.org/0000-0002-3953-5868)
- Muhammad Younus (ORCID: https://orcid.org/0000-0001-9889-9613)
- Haifeng Shu (ORCID: https://orcid.org/0000-0002-0193-1881)
- Yinglin Li (ORCID: https://orcid.org/0000-0002-2732-3040)
- Lianghong Zheng (ORCID: https://orcid.org/0000-0003-1119-7454)
- Zhongjun Qiao
- Li Zhou (ORCID: https://orcid.org/0000-0003-1945-3491)
- Qian Lei (ORCID: https://orcid.org/0000-0001-8647-1011)
- Quanfeng Zhang
- Min Gao (ORCID: https://orcid.org/0000-0001-5797-8905)
- Bing Liu (ORCID: https://orcid.org/0000-0002-6825-3536)
- Guoqing Chen (ORCID: https://orcid.org/0000-0001-7840-5719)
- Yuan Wang (ORCID: https://orcid.org/0000-0002-6324-6134)
- Jie Li (ORCID: https://orcid.org/0009-0005-5218-7625)
- Qinglong Wang (ORCID: https://orcid.org/0000-0003-1883-812X)
- Qihui Wu (ORCID: https://orcid.org/0000-0003-3762-2252)
- Shirong Wang (ORCID: https://orcid.org/0000-0002-6396-8292)
- Xi Wu (ORCID: https://orcid.org/0000-0002-9327-139X)
- Panli Zuo
- Shujiang Shang
- Yuqi Hang
- Zhaohan Lin
- Shu Guo
Institutions
- Peking University (CN)
- Southwest Medical University (CN)
- Chinese Institute for Brain Research (CN)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Center for Life Sciences (CN)
- Peking University Sixth Hospital (CN)
- Xi'an Jiaotong University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-12-27
- DOI
- https://doi.org/10.1002/advs.202412229
- Citations
- 4
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Shandong University
- National Natural Science Foundation of China
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
- China Postdoctoral Science Foundation
- Natural Science Foundation of Shanxi Province
- Peking University
- Hebei Medical University
- National Postdoctoral Program for Innovative Talents
- National Key Research and Development Program of China