Control of Male Mouse Copulatory Behavior by Midbrain Dopamine Neurons

Abstract

Ejaculation in male mice and humans requires intravaginal thrusting movements following penile intromission, yet the underlying neural mechanisms remain poorly understood. In this study, we used fiber photometry to record real-time activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of male mice during copulation across six sexual interactions, in order to investigate how these dynamics change with experience and to examine their functional significance. Contrary to expectations, phasic VTA DA activity remained stable across sessions, showing time-locked responses to mounts, penile intromission, individual thrusts, and ejaculation, indicating experience-independent neural representations of all copulatory events. Notably, thrusting-related activity sharply declined just before ejaculation. Optogenetic inhibition of DA neurons disrupted thrusting behavior, but did not block ejaculation, suggesting DA signaling is critical for sustaining copulatory actions rather than triggering ejaculation itself. While prevailing theories frame VTA DA activity as primarily experience-dependent or centered on reward prediction, we here highlight its role in behavioral persistence during copulation. More broadly, our findings extend understanding of DA function beyond classical reward paradigms to the regulation of innate complex, goal-directed behaviors.