Unraveling neuronal and molecular mechanisms of flexible social behavior in mice

Developmentally wired programs of social interactions in animals enhance reproductive success, yet these underlying neural circuits also allow for flexibility in behavior, such as modulating behavior in response to past experiences. The mechanisms enabling such flexibility in innate social behaviors remain poorly understood. This project aims to define the experience-driven neural mechanisms that enhance behavioral performance in male mating. We hypothesize that experiential changes in male mating are governed by neural plasticity within the circuits controlling this behavior, focusing specifically on preoptic hypothalamus neurons (POA) expressing tachykinin receptor 1 (POATacr1), a critical population that regulates male mating. To achieve our objectives, we will first delineate the afferent inputs onto POATacr1 neurons. We will employ retrograde tracing and optogenetic manipulations to identify and characterize cell populations projecting to POATacr1 and their role in mating. Second, we aim to elucidate the cellular and electrophysiological mechanisms underlying mating experience-driven plasticity. This includes measuring synaptic transmission onto POATacr1 neurons and characterizing mating experience-regulated cellular dynamics using in vivo 2-photon imaging. Furthermore, we will identify molecular pathways underlying mating experience-driven plasticity through deep sequencing to identify and functionally interrogate candidate genes regulated by mating experience. If successful, our project will reveal novel mechanisms underlying circuit plasticity during experientially driven changes in mating behavior, with potential implications for understanding reproductive behavior in health and disease. The interdisciplinary approach employed will provide insights into the interplay among genes, circuit plasticity, and innate behaviors, establishing a platform for future independent research. Project Number: 1K99HD118168-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Renzhi Yang | Institution: STANFORD UNIVERSITY, STANFORD, CA | Award Amount: $131,085 | Activity Code: K99 | Study Section: Reproduction, Andrology, and Gynecology Study Section[CHHD-R] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K99HD11816801