# The neuromolecular basis of adaptation to bond loss

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2024 · $477,216

## Abstract

Project Summary
Loss of a loved one elevates the risk for physical and mental illness and leads to impaired daily function. For
most people, the deleterious effects of loss improve with time. However, in a subset of bereaved individuals, the
failure to adapt leads to pathological manifestations of loss and an extension of bereavement-associated health
impairments. A lack of investigation into the neuronal and molecular processes that underlie healthy
adaptation to loss has hampered our ability to ameliorate the negative consequences of loss. To address this
gap in our understanding, we propose to use partner separation in monogamous prairie voles to operationally
produce loss. Socially monogamous prairie voles form life-long pair bonds and exhibit distress upon partner
separation. However, pairs bonds fade with time after partner separation, as evidenced by reduced bonding-
related behaviors. To identify the key neural and molecular changes that underlie the adaptive processes
engaged after loss of a partner, we will compare voles with intact partner bonds to those who have been
separated from their partner. In Aim 1, we will comprehensively assess behavioral and transcriptional
responses to partner separation over time. In Aim 2, we will ask how the molecular identity of the neurons
responsive to partner interaction changes as a function of separation time. Finally, in Aim 3 we will test the
hypothesis that ablation of partner-active neurons facilitates bond dissolution and enables the vole to form a
new bond. Together, these experiments will provide the first insights into key neuromolecular changes that
underlie adaptation to loss, thereby representing potential therapeutic targets for treating the negative aspects
of grief and Prolonged Grief Disorder.

## Key facts

- **NIH application ID:** 10746463
- **Project number:** 5R01MH125423-03
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Zoe Rebecca Donaldson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $477,216
- **Award type:** 5
- **Project period:** 2022-02-07 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746463

## Citation

> US National Institutes of Health, RePORTER application 10746463, The neuromolecular basis of adaptation to bond loss (5R01MH125423-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10746463. Licensed CC0.

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