# Central GLP1 Signaling Pathways and Anxiety

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $454,809

## Abstract

PROJECT SUMMARY/ABSTRACT
Affective anxiety is characterized by behavioral inhibition accompanied by cognitive arousal and vigilance,
reflecting a future-oriented emotional state. Anxiety is an adaptive response to perceived threat; however,
chronic anxiety is debilitating, and anxiety disorders are the most common type of mental illness in the United
States. Identification of neural circuits that underlie behavioral responses to threat in animal models is essential
for understanding neurobiological mechanisms that contribute to normative and pathological anxiety in
humans. Basic and clinical research has emphasized the importance of the central nucleus of the amygdala
(CEA) and the anterolateral bed nucleus of stria terminalis (alBST) in regulating affective and physiological
components of anxiety. The CEA and alBST are heavily interconnected and share many common sources of
input, including input from caudal brainstem neurons that convey sensory feedback from body to brain; this
feedback strongly modulates emotional state, including threat responses. The proposed research will test new
hypotheses regarding the organization and behavioral role of CEA/alBST-projecting brainstem neurons that
express glucagon-like peptide-1 (GLP1). GLP1 neurons are activated to express cFos in rats after acute threat,
and GLP1 receptor signaling in the CEA/alBST increases arousal/vigilance and behavioral inhibition/avoidance
in rats, akin to anxiety in humans. We recently developed a transgenic Sprague Dawley rat (Gcg-Cre) in which
Cre is efficiently and selectively expressed by GLP1 neurons in the caudal nucleus of the solitary tract and
intermediate reticular nucleus (i.e., NTS/IRtGLP1 neurons). Using validated viral tools and behavioral assays in
this new model organism, we will conduct comparative analyses of the synaptic connectivity and functional role
of NTS/IRtGLP1à CEA/alBST circuits in male and female Gcg-Cre rats, including documentation of potential sex
differences. Since the distribution of GLP1 neurons in brainstem and GLP1 receptors in limbic forebrain
appears similar in rats and humans, results from this basic science project have potential translational
relevance for understanding neurobiological bases of normal and pathological symptoms of anxiety in humans.

## Key facts

- **NIH application ID:** 10071677
- **Project number:** 2R01MH059911-22A1
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Linda M Rinaman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,809
- **Award type:** 2
- **Project period:** 1999-04-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071677

## Citation

> US National Institutes of Health, RePORTER application 10071677, Central GLP1 Signaling Pathways and Anxiety (2R01MH059911-22A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071677. Licensed CC0.

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