Post-inhibitory rebound firing promotes hypothalamic activation during male mating in mice.

During male mating, activation of the medial preoptic area (mPOA) and inhibitory input from the bed nucleus of the stria terminalis (BNST) are both required for mount initiation. How behaviorally relevant neural activation emerges in this limbic-hypothalamic circuit dominated by inhibition remains unclear. Here, using in vivo recordings, we show that mount-active mPOA neurons are suppressed before behavioral onset and that this pre-behavioral inhibition depends on BNST activity. Moreover, the magnitude of this inhibition predicts subsequent activation, consistent with post-inhibitory rebound firing (PIR). A biologically plausible conductance-based model shows that T-type Ca2+ currents, the ionic basis of PIR, interact with synaptic inhibition to promote mPOA activation. Bidirectional manipulation of T-type Ca2+ channel expression further supports this mechanism: knockdown reduces PIR, mPOA activity, and male mating, whereas overexpression enhances PIR and mating. Together, these results identify PIR as a mechanism by which inhibitory inputs gate hypothalamic activation during male mating.