Developmental and circuit mechanisms for innate social behaviors in the medial amygdala

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Project Summary Innate social behaviors are crucial for survival, thus shared across animal species. In humans, psychiatric disorders with deficits in social interactions include autism spectrum disorders and conduct disorder. Both of these conditions can be observed during early child development and have been associated with amygdala dysfunction. However, there is still a lack of understanding of the circuitry and developmental mechanisms for the generation of social behaviors; topics I aim to study in the long-term. To do so, I focus on the medial amygdala (MeA) as it is a region that has been implicated in both the processing of social olfactory cues and the generation of social motor actions in mice. The goal of this project is to uncover the neuronal circuitry for the sensory and motor processing of social behaviors, specifically aggression, and the developmental mechanisms for their establishment in male and female mice. I will take a developmental approach to study aggression by taking advantage of my previously characterized MeA neuronal subpopulation, marked by the expression of the embryonic and postnatal transcription factor Foxp2. MeA Foxp2+ cells are molecularly and physiologically distinct from other developmentally-defined subpopulations in the region. I present a central hypothesis in which there are sexually dimorphic differences in the sensory processing of social information arising during postnatal development in the MeA, resulting in specific downstream functional circuits. I will take a holistic approach and study sex-specific differences at distinct developmental trajectories and under different environmental conditions. In Aim 1 (K99), I will investigate the cellular responses and functions of MeA Foxp2+ cells in female mice during aggression and other social behaviors through the use of fiber photometry and chemogenetic tools. In Aim 2 (K99), I will establish the MeA Foxp2+ cells downstream projections in male and female mice to uncover sex-specific differences in the circuits for aggression. In Aim 3 (R00), I will study the developmental mechanisms for the generation of these circuits at distinct time-points pre-and post-puberty. I will also investigate how the circuit may be modified by early life adverse experiences. In the mentored phase of the award, I will complete a training plan to develop and strengthen technical skills for circuit dissection in adult and juvenile mice. By integrating a diverse set of convergent techniques, including multi-fiber photometry, circuit mapping and genetically encoded sensors across developmental time-points in male and female mice, this project will greatly advance our understanding of the developmental mechanisms for the establishment of sexually dimorphic circuits for social behaviors.