# The role of locus coeruleus hyperactivity and galanin in depressive behavior

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

PROJECT SUMMARY
Depression is a highly prevalent disorder, yet reliable treatments are currently lacking for many people.
Because the basic etiology of depression is not yet known, it is currently impossible to create therapeutics that
target its underlying neurobiological causes. Evidence from previous research suggests that dysregulated
hyperactivity of the noradrenergic locus coeruleus (LC), a brainstem nucleus that has been implicated in
neuropsychiatric disorders, may be causally involved in depression. Because norepinephrine transmission
itself can have antidepressant properties, it is likely that a different LC-derived neuromodulator is responsible.
Galanin is a neuropeptide that is enriched in LC neurons and has pro-depressant effects. Therefore, the
overarching hypothesis for this project is that LC hyperactivity and resulting galanin transmission can cause
depression-like behavior.
 The proposed project will combine optogenetic and in vivo electrophysiology techniques to modulate
and measure neuron activity with genetic approaches to manipulate galanin in behavioral assays of
depression-like behavior in mice. In Aim 1, I will use optogenetics to determine whether driving LC firing
frequencies that cause galanin release can induce depressive-like behavior in wild-type or genetically altered
mice with overexpression or depletion of LC-derived galanin. In Aim 2, I will assess the ability of
optogenetically-induced LC hyperactivity to alter the activity of ventral tegmental area (VTA) dopaminergic
neurons, which are thought to be compromised in depression-related behaviors, and determine the
contribution of galanin using the genetically altered mice described above. These experiments will be the first
to precisely test the causal relationship between LC hyperactivity and depression and determine the
contribution of LC-derived galanin and suppression of VTA dopamine neurons, which will help pave the way for
the development of effective, targeted therapeutics to treat people with depression.

## Key facts

- **NIH application ID:** 9984828
- **Project number:** 5F31MH116622-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rachel Catherine Pearcy Tillage
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-09-05 → 2021-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984828

## Citation

> US National Institutes of Health, RePORTER application 9984828, The role of locus coeruleus hyperactivity and galanin in depressive behavior (5F31MH116622-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9984828. Licensed CC0.

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