NIH grant: Neuromodulatory mechanisms mediating social attachment behaviors (1R01MH141154-01)

retained text

NIH grant 1R01MH141154-01: Neuromodulatory mechanisms mediating social attachment behaviors
Institute: {'code': 'MH', 'abbreviation': 'NIMH', 'name': 'National Institute of Mental Health', 'admin_org_id': '12500050', 'admin_funding_url': ''}. PI: Devanand Sadanand Manoli. Award: $819283.
Start: 2026-08-01T00:00:00.
PROJECT SUMMARY
Social attachments play a central role in most, if not all, levels of human interaction, from parent-child attachment
to enduring partnerships with mates. Many neuropsychiatric disorders manifest with severe disruptions to
interpersonal interactions, significantly impacting health and relationships. Despite the importance of attachment,
little is known about the neural pathways mediating these behaviors, or how they are impacted by environmental
or genetic factors that disrupt relationships. Prairie voles (Microtus ochrogaster) form social attachments to their
mates (pair bond) and demonstrate enduring social monogamy. Pair bonded prairie voles prefer huddling with
their partners and aggressively reject other potential mates, providing a powerful system to understand the
fundamental mechanisms that mediate the formation and expression of enduring attachments. Pioneering work
identified the peptide hormones vasopressin (Avp) and oxytocin (Oxt) as critical mediators of pair bonding and
complex social behaviors in diverse species, including humans. The deep similarity in genetic and
neuroanatomic structures between humans and other eutherian mammals and the conserved roles of these
hormones throughout vertebrates suggests that findings in the prairie vole model may inform our understanding
of human attachment behaviors.
 To understand behavioral modules underlying social attachment and their genetic, molecular, and neural
architecture, we developed 1) a rigorous battery of social behavior paradigms, 2) tools for genomic analysis, and
3) in vivo imaging approaches to monitor neural activity, coupled with 4) molecular genetics in prairie voles, to
analyze distinct components of attachment behaviors. Our recent work has revealed previously unappreciated
nuances in the neuromodulatory control of pair bonding. We find that signaling by the oxytocin (Oxtr) and
vasopressin 1a receptors is strikingly not required for the formation of partner. Rather, Oxtr function controls the
timing and promiscuity of pair bonding and influences reciprocal social interactions between mates. Using
unbiased profiling of gene expression, characterization of expression changes in components of various
neuromodulatory pathways, in vivo imaging of the activity of other neuromodulatory systems, and pharmacologic
manipulations of these pathways in specific brain regions, we find that separate signaling pathways appear to
regulate distinct components of social attachment behaviors. Here, we extend these studies to determine how
these and other neuromodulatory pathways act, and interact, in specific brain regions across the formation of
bonds and subsequent social interactions to influence enduring social relationships between mates.

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