Sequential transitions of male sexual behaviors driven by dual acetylcholine-dopamine dynamics
The neural mechanisms underlying the sequential transitions of male sexual behaviors, including mounting, intromission, and ejaculation, remain largely unexplored. Here, we report that acetylcholine (ACh)-dopamine (DA) dynamics in the ventral shell of the nucleus accumbens (vsNAc) regulate these sexual transitions in male mice. During intromission, the vsNAc displays a unique pattern of dual ACh-DA rhythms, generated by reciprocal regulation between ACh and DA signaling via nicotinic ACh receptors (nAChRs) and DA D2 receptors (D2Rs). Knockdown of choline acetyltransferase (ChAT) or D2R in the vsNAc diminishes the occurrence of intromission and ejaculation. Optogenetic manipulations demonstrated that DA signaling maintains sexual behaviors by suppressing D2R<sup>vsNAc</sup> neurons. Moreover, ACh signaling promotes the initiation of mounting and intromission and facilitates the intromission-ejaculation transition by inducing a slowdown in DA rhythm. Together, these findings reveal that coordinated ACh-DA dynamics in the vsNAc play a critical role in orchestrating the sequential transitions of male sexual behaviors.
Authors
- Masashi Yanagisawa (ORCID: https://orcid.org/0000-0002-7358-4022)
- Yoan Chérasse (ORCID: https://orcid.org/0000-0002-6139-8193)
- Jun Seita (ORCID: https://orcid.org/0000-0002-3008-3615)
- Yukiko Ishikawa (ORCID: https://orcid.org/0000-0003-2688-0782)
- Yuka Terakoshi (ORCID: https://orcid.org/0009-0000-5744-9624)
- Arisa Hirano (ORCID: https://orcid.org/0000-0001-9732-6100)
- N. Nonaka
- Hotaka Takizawa (ORCID: https://orcid.org/0000-0002-5703-2535)
- Ai Miyasaka (ORCID: https://orcid.org/0000-0002-8231-4358)
- Qinghua Liu (ORCID: https://orcid.org/0000-0002-5996-0634)
- Yulong Li (ORCID: https://orcid.org/0000-0002-9166-9919)
- Takeshi Sakurai (ORCID: https://orcid.org/0000-0003-4474-6253)
- Takeshi Kanda (ORCID: https://orcid.org/0000-0001-8470-7051)
- Katsuyasu Sakurai (ORCID: https://orcid.org/0000-0002-7729-3169)
Institutions
- University of Tsukuba (JP)
- Peking University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- RIKEN Center for Advanced Intelligence Project (JP)
- Nara Medical University (JP)
- Tsukuba International University (JP)
Publication Details
- Journal
- Neuron
- Published
- 2025-03-19
- DOI
- https://doi.org/10.1016/j.neuron.2025.01.032
- Citations
- 9
- Primary Topic
- Neuroendocrine regulation and behavior
- Type
- article
- Field-Weighted Citation Impact
- 21.95
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science