BRC-BIO: Molecular identity and function of neuronal cell types underlying social thermoregulation.

The ability to maintain body temperature within a narrow range is essential for survival. When exposed to cold, mammals generate heat through metabolic processes and seek warmth through behaviors such as huddling. Huddling—an active and close congregation of animals—is an effective strategy for conserving energy and maintaining warmth. While much is known about how the brain regulates physiological responses to cold, little is understood about how it governs behavioral strategies like huddling. This research aims to uncover how the brain integrates signals from other individuals and physiological cues to regulate body temperature. The study will identify the specific brain cells involved in huddling behavior and determine how they contribute to temperature regulation. By investigating these neurons and their connections this research will enhance our understanding of how the brain balances interactions with other individuals with basic survival needs. The results have broad implications, from fundamental knowledge of body regulation to improved understanding of disorders associated with disruptions of both conspecific behavior and temperature control. This project will also provide research training opportunities for students, contributing to a better-prepared workforce. Additionally, outreach efforts will engage high school students in neuroscience, inspiring future generations of scientists. This project investigates the neural circuits that govern huddling as a form of behavioral thermoregulation in the laboratory mouse, Mus musculus. While the hypothalamic-brainstem circuits controlling autonomic thermoregulation are well characterized, the neural mechanisms underlying behavioral responses to temperature remain largely unknown. The central hypothesis of this study is that specific neural pathways regulate huddling behavior to maintain thermal homeostasis. Our preliminary findings indicate that huddling-associated neurons are present in the dorsomedial (DMH), posterior (PH), and paraventricular (PVN) regions of the hypothalamus. Additionally, this group has identified cold-activated neurons expressing the oxytocin receptor in the rostral medullary raphe (rMROXTR)—a key brainstem region for thermoregulatory control. Building upon these findings, our study has two objectives: (1) to determine the molecular identity of huddling-associated neurons in the hypothalamus using single nucleus RNA sequencing (snRNA-seq) and histology, and (2) to assess the functional role of rMROXTR neurons in thermoregulatory behavior and autonomic responses through chemogenetic manipulations. This research integrates neurogenetics, behavior, and physiology to elucidate the mechanisms by which individual interactions contribute to homeostatic regulation. The findings will advance understanding of how social behavior and physiological needs are interconnected in the brain and may provide insights into neuropsychiatric disorders characterized by disruptions in behavior and thermal regulation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.