# Systematic characterization of social attachment behaviors and their underlying molecular substrates

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $135,426

## Abstract

PROJECT SUMMARY
 Social attachments form the basis of human relationships at every level of social organization, from
relationships between parents and children, romantic partners, to peers and group affiliation. Disruptions in
attachment occur across the spectrum of mental illness, and severe neuropsychiatric disorders often manifest
with a dramatic collapse of social attachment and cognition. Despite this critical role of social attachment, little is
known regarding the neural and genetic mechanisms underlying attachment. Mice and other genetic model
organisms do not exhibit enduring social attachments, precluding genetic analysis of these behaviors.
 Prairie voles are small rodents that display social monogamy, or pair bonds, between mates. Pair bond
formation results in dramatic changes to many other innate social behaviors. Thus, prairie voles engage in a rich
repertoire of social behaviors that strikingly mirror attachment in humans. Pioneering work identified the peptide
hormones vasopressin (Avp) and oxytocin (Oxt), as critical mediators of pair bonding in voles and social cognition
and behaviors in humans. These findings suggest that the genetics and neural control of social attachment may
be conserved, and indeed, have inspired clinical trials seeking to use these hormones to ameliorate disruptions
in social cognition due to neuropsychiatric conditions. Nevertheless, how these pathways and other genes
function to control specific aspects of complex social behaviors remains unknown.
 Until now, we have been unable to understand how OxtR and V1aR function to control patterns of neural
activity in response to partners or strangers. We have generated prairie voles bearing mutations in OxtR and
V1aR that completely eliminate the function of these receptors, and developed approaches for optical recording
of neural activity in freely moving animals during behavior and profiling of gene expression in prairie voles. Using
this powerful system, we can now test the hypothesis that OxtR and V1aR control distinct aspects of 1) pair
bonding and adult social attachment behaviors, 2) partner- or stranger-specific patterns of neural activity in
specific regions of the vole brain during social interactions, and 3) changes in gene expression underlying social
attachment in these neural populations. Our preliminary work suggests that OxtR signaling is not required
genetically for pair bonding in prairie voles, and, thus, that a more refined understanding of the neural and
molecular pathways underlying social attachment may provide new insights into the pathways that mediate the
formation of such long term social memory and affiliation. These studies will elucidate the mechanisms by which
OxtR and V1aR facilitate attachment and, eventually, inform new therapeutic approaches across the spectrum
of mental illness.

## Key facts

- **NIH application ID:** 10599761
- **Project number:** 3R01MH123513-03S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Devanand Sadanand Manoli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $135,426
- **Award type:** 3
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599761

## Citation

> US National Institutes of Health, RePORTER application 10599761, Systematic characterization of social attachment behaviors and their underlying molecular substrates (3R01MH123513-03S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10599761. Licensed CC0.

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