Social Isolation Re-Organizes Neural Dynamics Governing Mating - PROJECT SUMMARY/ABSTRACT Animals deprived of social contact for an extended period of time exhibit a myriad of deleterious effects on the brain and behavior. One of the most striking impacts of prolonged social isolation is its ability to disrupt reproductive behavior across species. Indeed, isolation has been shown to negatively impact mate selection, sexual frequency, and reproductive success. In humans, social isolation or its perception, “loneliness”, has been linked to domestic violence, divorce, poor sexual health, low relationship satisfaction, depression, infertility, and more. Despite the clear relevance to public health, the brain mechanisms and neural dynamics underlying prolonged social isolation and its impact on reproduction are largely unknown, representing a critical gap in the field. Combining machine learning with innovative, integrative computational approaches, in-depth behavioral analyses, acoustic recordings, cell-type specific functional manipulations, and in vivo microendoscopic imaging of neural activity in male and female mice, we will close this gap in knowledge. We will determine the role of neuropeptide signaling within the hypothalamus to control the effects of isolation on reproduction (Aim 1), establish how neural activity is re-organized by social isolation (Aim 2), and reveal the impact of male isolation on conspecific female behavior and neural activity (Aim 3). Collectively, these aims will allow us to test the overarching hypothesis that social isolation alters mating via scalable action of genetically-defined neurons deep in the hypothalamus. If the aims of this project are achieved, we will have uncovered fundamental principles about how circuit mechanisms govern internal brain states such as social isolation. We expect that our findings will significantly impact the treatment of social isolation-related disturbances to public health, including domestic violence, dysregulated sexual behavior, social disconnection, and infertility.
