Circuit Mechanisms of Social Attachment in the Prairie Vole Medial Amygdala

/ Abstract Enduring social bonds are essential for human health and well-being, yet their underlying neural mechanisms remain elusive due to limitations in traditional model organisms. Prairie voles, which naturally form lifelong pair bonds, offer a powerful system for investigating how the brain encodes stable social states. The medial amygdala (MeA) is functionally connected to a broad network of brain regions that collectively governs social behavior. Specifically, the MeA relays pheromonal cues that are critical for guiding context- appropriate behavior selection, yet how this region contributes to the behavior transition from a naïve to a bonded state in prairie voles is unknown. This proposal investigates how molecularly defined circuits in the MeA contribute to the emergence and maintenance of attachment behavior. Using single-cell RNA sequencing, I identified a sex-biased neuronal population that downregulates the neuropeptide gene Tac1 following pair bond formation. Intriguingly, the mouse equivalent of this population drives both affiliative and aggressive behaviors, and Tac1 itself has been linked to aggression control. In prairie voles, a bonded animal exhibits selective affiliation toward its partner and aggression toward all other opposite-sex conspecifics – a behavioral dichotomy that may be orchestrated by this population. I propose to characterize how this population is integrated into broader brain circuits of prairie voles and to monitor its activity during the formation of a pair bond. These experiments will clarify whether and how this population might serve as a neural substrate for the internal state of bondedness. Ultimately, this research may shed light on fundamental principles of social attachment and offer insight into how disruptions in such processes contribute to psychiatric illness. In addition to the proposed research, this application outlines a comprehensive training plan to prepare Dr. Wang for an independent career as a neuroscientist and psychiatrist. She will be mentored by Dr. Dev Manoli (UCSF), an expert in the molecular genetics and social behavior of prairie voles, and co-mentored by Dr. Michael Brainard (UCSF), a leader in the neurophysiology of complex behavior, and Dr. Vikaas Sohal (UCSF), who specializes in quantitative neural data analysis and circuit-level manipulations. Dr. Wang will also receive guidance on advanced molecular tool development from Dr. Nadav Ahituv (UCSF) and Dr. Josh Huang (Duke). Her career development is strongly supported by the UCSF Department of Psychiatry and Behavioral Sciences, which is committed to transitioning her to a full-time faculty position. Project Number: 1K08MH144328-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Shuyu Wang | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $209,520 | Activity Code: K08 | Study Section: Special Emphasis Panel[ZRG1 BP-R (81)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11352889