Structural and functional connectivity of the social decision-making network

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Humans and numerous other species live in complex social environments, requiring many of our most important decisions to be made in the context of social interactions. All of our social relationships rely on our ability to make context-appropriate decisions, including significant ties with committed partners, family, and friends. The social decision-making (SDM) network hypothesis suggests that the expression of a given social behavior is reflected by the overall activity of a network of structures rather than activity of any single structure. Although the SDM network has been proposed on functional grounds, most of the supportive evidence is based on structural connectivity among loci and on examining the function of individual neurochemicals, brain areas, and neuronal mechanisms therein. We know surprisingly little about network function that regulates context-appropriate social behaviors. The socially monogamous prairie vole (Microtus ochrogaster) provides an opportunity to examine the neural mechanisms underlying social decisions which foster intimate relationships through the study of brain circuits regulating behavioral choices in interactions with current and potential partners. Our long-term goals are to dissect the neurocircuitry of social behavior (including the social behavior network and mesolimbic reward system), define normal and aberrant network activity during context-appropriate and context-inappropriate behaviors, respectively, and develop precise interventional tools that change circuit dynamics. Our theoretical neurocircuit of pair bond behaviors centers in five brain structures within the SDM network demonstrated to have functional specialization in regulating partner-directed affiliative behaviors, stranger-directed aggressive rejection, or both. Our specific aims will test the following hypotheses: (AIM 1) structural and functional connectivity between brain regions will vary depending on type of social stimuli and pair bond status; (AIM 2) Real-time recording in the SDM network will demonstrate that regional and interregional neural firing is distinct during (a) affiliative vs aggressive, (b) familiar vs unfamiliar, and (c) preferred vs non-preferred social interactions; and (AIM 3) altering neurochemical inputs into and activation of select projections out of a central hub will promote shifts in activity across the neural network and adjust what is considered context-appropriate behaviors. Upon conclusion, we will understand the role of regional and interregional activity within a network which governs behavioral choices that either enhance or marginalize intimate social ties. This contribution is significant as it will be the first study to utilize such time-sensitive measurements of neural activity within the SDM network in freely- moving voles and will service as a proof-of-concept for how this neural network guides decisions in other social scenarios which impact our most important social relationships. The proposed research is innovative as it employs simultaneous fast measurement and manipulation of neural activity of the SDM network to better address many aspects of network connectivity and integrates new technologies into in vole research, which may serve as a template for how these technologies can be adapted for other non-traditional animal models.