The central goal of this work is to identify the configurations of neural circuit anatomy and function that support social behavior in males and females. Social behavior requires efficient integration of sensory cues from the external environment with an animal's internal physiology and neuroendocrine state. These computations often vary such that a single social stimulus can elicit markedly different behaviors in male and female animals. Here, we seek to establish how unique patterns of circuit connectivity shape sexually dimorphic circuit function. We will focus on aromatase?expressing neurons and estrogen receptor alpha?expressing neurons in the extended amygdala. The mouse is an ideal species for revealing the contribution of genetically defined populations of neurons to social behavior. In people, sex differences in behavior likely arise from complex interactions of biology and past experiences, but our social behavior networks share a deep evolutionary history with other vertebrates. In mice, reproducible sex differences in the size of specific populations of neurons, patterns of gene expression, targets of axonal projections, and dendritic architecture are well-established. When paired with powerful tools for genetic manipulation, these populations of neurons provide a unique opportunity for a systematic investigation of the relationships between neuroanatomical variation (at the level of circuits) and sex differences in behavior. Because the specific circuit configurations for either target population are not yet known in males or females, Aim I will use rabies tracing to map these circuits with an eye toward quantifying sexually dimorphic wiring patterns.
Aim II investigates the neurochemical phenotype of neurons that provide input to aromatase- expressing and estrogen receptor alpha?expressing neurons in the extended amygdala. Quantifying the neurotransmitters used in these circuits will help us understand how activity at one node influences activity in its synaptically coupled partners.
Aim III explores the moment-to-moment activity of these neural populations to reveal their respective contributions to processing social stimuli and producing social behavior. Together, these studies will advance our mechanistic understanding of how social information is transformed into sexually dimorphic cognitive, endocrine, and behavioral outputs.
Medical treatments that account for sex-differences in brain function require a mechanistic understanding of the underlying neural circuits. Many human conditions ? including autism, anorexia, depression, and schizophrenia ? are sexually dimorphic in incidence, severity, and symptomology. The experiments outlined in this proposal will give us insights about how neural circuits are differentially regulated in male versus female animals with a long-term goal of understanding the factors that differentially regulate neural circuits during sickness and health.
