Synaptic connections of aromatase circuits in the medial amygdala are sex specific

Abstract

The brain of male and female mice is shaped by genetics and hormones during development. The enzyme aromatase helps establish sex differences in social behaviors and in the neural circuits that produce these behaviors. The medial amygdala of mice contains a large population of aromatase neurons and is a critical hub in the social behavior network. Moreover, the neural representation of social stimuli in the medial amygdala displays clear sex differences that track developmental changes in social behaviors. Here, we identify a potential anatomical basis for those sex differences. We found that sensory input from the AOB to aromatase neurons is derived nearly exclusively from the anterior AOB, which selectively responds to chemosensory cues from conspecific animals. Through the coordinated use of mouse transgenics and viral-based circuit tracing strategies, we demonstrate a clear sex difference in the volume of synapses connecting the accessory olfactory bulb to aromatase-expressing neurons in the medial amygdala of male versus female mice. This difference in anatomy likely mediates, at least in part, sex differences in medial amygdala mediated social behaviors.

Significance statement The medial amygdala is a central hub of the brain’s social behavior network that integrates social information and produces behaviors like aggression, parenting, and reproduction. We determined that in mice, medial amygdala neurons expressing aromatase – an enzyme that converts testosterone to estradiol and plays an important role in establishing neuroanatomical sex differences – receive sensory information from a restricted population of pheromone-sensitive neurons in the vomeronasal pathway. These aromatase-expressing neurons had similar intrinsic electrophysiological properties in both sexes but received more sensory inputs in males than in females. We propose that the different anatomical configurations of social circuits described here contribute to known sex differences in medial amygdala function and, ultimately, to sex differences in critically important social behaviors.