# The role of hypothalamic oxytocin signaling in defeat-induced social learning

> **NIH NIH U19** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $585,110

## Abstract

Project Summary (Project 2, Co-PIs: Lin, Buzsaki, Froemke, Tsien)
In a complex social group, the ability to learn who to approach and who to avoid is essential for success or even
survival. Mice, just like humans, quickly learn to avoid a bully after they are attacked and defeated. This defeat-
induced social learning is essential for establishing stable social hierarchies. Animals learn their ranking relative
to a competitor after each round of fighting. This iterative process leads to a “pecking order”. The neural
mechanisms supporting the behavioral change after social defeat remain elusive. The goal of Project 2 is to
understand the neural process underlying social learning in the context of social hierarchy formation, with a
special focus on oxytocin. Our recent study found that oxytocin signaling in a small hypothalamic region, the
anterior ventrolateral part of ventromedial hypothalamus (aVMHvl), is essential for defeat-induced social
learning. Specifically, in defeated animals, oxytocin receptor (OXTR)–expressing cells in the aVMHvl
(aVMHvlOXTR) specifically increase responses to cues generated by the winner. This increase is functionally
important as inactivation of VMHvlOXTR cells impairs avoidance of the winner, whereas optogenetic activation of
the cells induces avoidance even in undefeated animals. We further found that OXTR in the aVMHvl is itself
necessary for the defeat-induced social avoidance thanks to its role in facilitating synaptic potentiation.
Interestingly, aVMHvlOXTR cells receive a private source of oxytocin from the nearby retrochiasmatic supraoptic
nucleus (SOROXT), which is activated during defeat and functionally important for defeat-induced behavioral
changes.
 Following up on these exciting findings, our current proposal is aimed at deepening and broadening our
understanding of OXTR signaling in social learning in the context of social hierarchy formation via three specific
aims. Aim 1 will address whether OXTR signaling is essential for the initial social learning (memory formation)
or remembering after learning (memory retention). Aim 2 will test the hypothesis that social status modulates
OXTR signaling at the aVMHvl to adjust rate of social avoidance learning, i.e., susceptibility to defeat. Lastly, in
Aim 3, we will examine the role of OXTR signaling in forming and maintaining social hierarchies through long-
term behavior recording, genetic manipulation, and computational modeling, requiring the essential services of
each Core facility proposed in this U19. This project draws diverse expertise from all U19 PIs and cores, using
tools including transcriptomic profiling, in vivo and in vitro recordings, functional manipulations, and theoretical
modeling. This Project provides critical data on adult social interactions important for communal living/parenting
for Project 1, relies on mechanistic studies and data to be performed in Project 3, and serves as a test-bed for
circuit-level perturbations developed in Pr...

## Key facts

- **NIH application ID:** 10912578
- **Project number:** 5U19NS107616-07
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Dayu Lin
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $585,110
- **Award type:** 5
- **Project period:** 2018-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912578

## Citation

> US National Institutes of Health, RePORTER application 10912578, The role of hypothalamic oxytocin signaling in defeat-induced social learning (5U19NS107616-07). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10912578. Licensed CC0.

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