# The PACAP signaling pathway as a novel regulator of the neural circuits underlying fear generalization

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,036

## Abstract

Project Summary / Abstract
Anxiety disorders, such as generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD), are
the most common mental illnesses in the US, affecting up to 18% of the general population. A defining symptom
of these disorders is fear generalization, in which learned fear responses are transferred to similar but novel
stimuli. Examining the neural circuits that modulate fear generalization and context discrimination is therefore a
critical step to understanding the neural substrates of stress resilience. The neuropeptide pituitary adenylate
cyclase-activating peptide (PACAP) is known as a critical regulator of fear responses in the brain and periphery.
PACAP acts on several different receptors in the brain, including pituitary adenylate cyclase-activating
polypeptide type I receptor (PAC1) and vasoactive intestinal peptide receptor 2 (VPAC2). This Kirschstein-NRSA
F31 application presents a program for research and training that will support me on a path towards developing
the skills necessary to become an independent research scientist focused on studying PACAP and VPAC2
signaling and their effects on fear generalization using cutting-edge techniques such as whole-brain imaging,
and simultaneous optogenetic manipulation and in vivo Ca2+ imaging. In this proposal, I will investigate how
whole-brain VPAC2 expression correlates with the behavioral output of fear generalization (Aim 1), and assess
the contribution of VPAC2 in altering activity of the neural circuits underlying fear generalization (Aim 2). In Aim
1, mice will be assayed using a contextual fear discrimination (CFD) task. Whole-brain imaging techniques will
then be used to visualize and compare brain-wide VPAC2 expression between populations of high- and low-fear
generalizing mice. In Aim 2, I will leverage the Inscopix nVoke system for simultaneous in vivo optogenetic and
Ca2+ imaging during real-time CFD behavior to investigate how VPAC2 modulates neural activity to affect fear
generalization behavior. Successful completion of this study will help elucidate the role of a novel signaling
pathway in mediating the neural substrates of fear generalization. Ultimately, this knowledge could contribute to
the development of more targeted, specific interventions to better treat and prevent fear and anxiety disorders.
These data, along with the research and scientific expertise developed through this F31 award, will support my
successful transition into an independent neuroscientist.

## Key facts

- **NIH application ID:** 10163069
- **Project number:** 5F31MH121023-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Briana Kaying Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163069

## Citation

> US National Institutes of Health, RePORTER application 10163069, The PACAP signaling pathway as a novel regulator of the neural circuits underlying fear generalization (5F31MH121023-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163069. Licensed CC0.

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