Post-ejaculatory Inhibition of Female Sexual Drive via Heterogeneous Neuronal Ensembles in the Medial Preoptic Area

Abstract

SUMMARYThe completion of mating acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how the completion of mating affects sexual motivation and sexual behavior in female mice. How the brain responds to completion of mating is also unclear. Here, by using self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation after the completion of mating. By using brain-wide analysis of activity-dependent labeling, we next pin-pointed the medial preoptic area as a brain region strongly responding to mating completion. Furthermore, using freely movingin vivocalcium imaging to compare neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of neurons responds significantly and specifically to mating completion but not to appetitive or consummatory behaviors. While there were excitatory and inhibitory neurons that showed positive response to the completion of mating, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of the completion of mating. These neurons were all inhibitory indicating that the completion of mating induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that respond to mating completion, but not to appetitive behaviors, was sufficient to suppress female sexual motivation. Together, our data illuminate the importance of medial preoptic area as a brain node which encodes a negative signal that sustains low sexual motivation state after the completion of mating in female mice.HighlightsFemale mice show decreased sexual motivation after mating completion.A subset of MPOA neurons respond specifically to mating completion.Mating completion evokes persistent activity in MPOA inhibitory neurons.Activation of a subset of MPOA neurons is sufficient to suppress female sexual motivation.

Hormonal and circuit mechanisms controlling female sexual behavior

“…Investigating the activity dynamics of neural populations responsible for rejection during mating completion, and vice versa, could offer valuable insights into the similarities and differences between these behaviors and states. As described, a subpopulation of mPOA neurons has been identified to encode mating completion ( Ishii et al, 2023 ). Interestingly, another subpopulation of mPOA neurons, Galanin + mPOA neurons, undergo significant plastic changes during pregnancy, contributing to parenting behavior post-delivery ( Ammari et al, 2023 ).…”

“…However, causal relationships of these populations in copulation remained elusive. Recently, Ishii et al (2023) discovered that a subset of GABAergic neurons in the mPOA reacts to the completion of mating, specifically when a female receives male ejaculation. These neurons were identified and labeled separately from those activated by pre-mating attractive behavior, allowing for targeted investigation into their respective roles in modulating female sexual behavior.…”