# Contribution of the Parabrachial CGRP-Expressing Neurons to the Pathophysiology of Panic Disorder

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2022 · $581,475

## Abstract

Project Summary/Abstract
Panic disorder is a debilitating anxiety disorder that is characterized by sudden and recurrent attacks of
intense, uncontrollable anxiety and fear. This psychiatric illness is unique among other anxiety-related
disorders because individuals with panic disorder not only experience mental symptoms during an attack, but
they also suffer acute physical symptoms, including cardiorespiratory, autonomic, and gastrointestinal
symptoms. In addition, these panic attacks occur spontaneously, and are associated with innate unconditioned
fear (i.e., fear that has not been learned through an aversive experience). To understand what causes these
bouts of unconditioned fear and associated physiological symptoms in panic disorder, it is critical to
characterize the neural circuitry underlying innate threat perception. The lateral parabrachial nucleus (PBN)
within the brainstem regulates cardiorespiratory and autonomic functions, and also relays multimodal aversive
sensory signals to the amygdala. Preliminary data show that factors that induce panic attack in panic disorder
patients, such as caffeine, yohimbine or high CO2 levels, robustly activate neurons in the external lateral region
of the PBN (PBel) that express a particular neuropeptide, Calcitonin gene-related peptide (CGRP), and
activation of these neurons is necessary and sufficient for innate threat perception. However, little is known
about the circuit mechanism of the PBel CGRP-expressing neurons in panic disorder pathogenesis. To
address this problem, proposed experiments use state-of-the-art neural circuit dissection tools to MONITOR
and MANIPULATE the activity of PBel CGRP neurons, as well as target neurons that express the CGRP
receptor. The central objective of this proposal is to determine how PBel CGRP neurons respond to and
encode innate sensory threats, and how these neurons contribute to the unique physical and emotional
comorbidities in panic disorder. To achieve this objective, activity of PBel CGRP neurons will be monitored (via
in vivo calcium imaging) as mice are exposed to multimodal sensory threats or panicogenic agents (Aim 1).
PBel CGRP neurons will then be manipulated (inhibited or activated) using optogenetic and chemogenetic
techniques to establish causal relationships between CGRP neuronal activity and physiological changes during
innate threat perception (Aim 2). Lastly, activity of downstream neurons (those that express CGRP receptors in
brain regions innervated by PBel CGRP neurons) will be monitored and manipulated to establish functional
neural circuits involved in panic disorder pathogenesis (Aim 3). Contributions of the proposed research will be
significant because it will advance the circuit-level understanding of panic disorder pathogenesis. The research
plan is innovative because it investigates, for the first time, involvement of the PBel in panic disorder
pathogenesis using cell type-specific circuit dissection tools. Successful completion of...

## Key facts

- **NIH application ID:** 10335187
- **Project number:** 5R01MH116203-05
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Sung Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $581,475
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335187

## Citation

> US National Institutes of Health, RePORTER application 10335187, Contribution of the Parabrachial CGRP-Expressing Neurons to the Pathophysiology of Panic Disorder (5R01MH116203-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10335187. Licensed CC0.

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