Neural Circuit Dissection of Prefrontal Cortex Projections in Social Dominance Behavior

项目总结/文摘

Project Summary/Abstract Social interactions, reciprocal interactions between two or more individuals, are critical to the physical and emotional health of a wide variety of species. Perturbations in social functioning, a hallmark symptom of many psychiatric and neurodevelopmental disorders such as autism and schizophrenia, can profoundly impair an individual's ability to sustain healthy social relations. However, while disruption in social behavior can arise as a symptom of such disorders, negative social experiences, such as exposure to antagonistic or dominant social agents, can also support the development and maintenance of psychiatric disorders, such as depression and anxiety. Furthermore, expression of dominance behavior during social interactions is strongly linked to resilience to psychiatric disorders in both rodents and humans—individuals who assert dominance are more resilient to depressive-like symptoms, while individuals who display subordinate behaviors are more vulnerable to the debilitating effects of stress. Despite growing evidence of the role that social dominance plays in the etiology of psychiatric disorders, our current understanding of the neural circuit mechanisms that promote dominant and subordinate behaviors remains remarkably weak. Published work from our lab and others has identified the dorsomedial prefrontal cortex (dmPFC) as a critical node for the expression of dominance behaviors in both rodents and humans. However, how neural computations in the dmPFC that orchestrate social dominance decisions are relayed to subcortical limbic regions has never been explored. The experiments described in this proposal will fill a critical gap in our understanding of neural mechanisms for dominance behavior by performing detailed neural circuit dissection strategies to anatomically map, physiologically observe, computationally model, and functionally manipulate individual descending projections of the dmPFC during social dominance behaviors. Specifically, the outlined proposal will 1) utilize in vivo optogenetics to bidirectionally manipulate dmPFC projections during social dominance behaviors and 2) utilize in vivo freely moving calcium imaging to optically record projection-defined dmFPC populations during dominance decisions. The proposed study will reveal how discrete, anatomically-defined pathways descending from the dmPFC are engaged during social dominance. These results will set the foundation for a more incisive analysis of how dmPFC circuits shape social function in both health and disease.