# Stress induced plasticity of excitatory inputs to the LC

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $427,625

## Abstract

Stress related disorders, including anxiety and post-traumatic stress disorder (PTSD), are major unmet
clinical problems that have a higher prevalence and severity in females. The locus coeruleus
norepinephrine (LC-NE) system is a sexually dimorphic brain region and a key area activated by stressful
stimuli. Through its projections, the LC-NE system forms a major component of circuits that encode
behavioral responses to stress. Dysfunctions in the LC-NE system are associated with a variety of stress-induced neuropsychiatric disorders, including PTSD. While it is well known that the LC plays a central role
in stress-related behaviors, it remains unclear what inputs drive LC neuron excitability and how they
regulate this system in response to stress. At present, studies examining the LC have primarily focused on
stress-related peptides such as corticotropin releasing factor (CRF). The release of these peptides within
the LC has been shown to be a central factor that drives the LC during stress and is responsible for
mediating stress-induced anxiety-like behaviors. The mechanisms by which CRF mediates its effects in the
LC however are poorly understood. Despite the importance of CRF and the LC-NE system, few studies
have attempted to determine how CRF drives long-term changes in LC neuron excitability. The objective of
this proposal is to identify glutamatergic inputs to the LC, determine how they are regulated by CRF and
determine how the strength of these inputs is altered following stress. By comparing males and females and
examining the role that CRF plays in driving this plasticity, the wide-ranging importance of this work will be
to define the circuitry driving LC-NE activation by exposure to anxiety-inducing stressful stimuli.

## Key facts

- **NIH application ID:** 9994583
- **Project number:** 1R21MH123085-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Christopher Peter Ford
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,625
- **Award type:** 1
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994583

## Citation

> US National Institutes of Health, RePORTER application 9994583, Stress induced plasticity of excitatory inputs to the LC (1R21MH123085-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9994583. Licensed CC0.

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