# Identification of Brain Circuits Underlying Fear and Panic

> **NIH VA IK2** · IOWA CITY VA MEDICAL CENTER · 2024 · —

## Abstract

Objective: The objective of this proposal is to train Dr. Aubrey Chan, MD/PhD, dual-boarded in internal
medicine and psychiatry, to become an independent VA physician-scientist. He will be mentored in state-of-
the-art neuroscience research techniques in recording neural signals by his mentors Drs. Rainbo Hultman and
Nandakumar Narayanan, and he will be mentored in the cutting-edge analytical techniques applied to these
signals by Dr. Matthew Howard. Dr. John Wemmie will serve as the career development mentor, providing
guidance in Dr. Chan’s development as a principal investigator, managing lab personnel, mentoring graduate
students, scientific communication, and grantsmanship.
 These research techniques will be applied to a novel, circuit-wide analysis of defensive responses by
recording from and analyzing signals of multiple brain regions simultaneously. Defensive responses are
physiological, emotional, and behavioral changes that occur when an organism is faced with a threat.
Excessively active or exaggerated defensive responses underlie psychiatric illnesses like post-traumatic stress
disorder, an illness that is highly prevalent in the veteran population, and which causes tremendous distress,
disability, and suicide in veterans. Defensive responses will be studied in mice in response to carbon dioxide
(CO2), a naturalistic stimulus which represents the interoceptive (internal) threat of suffocation. This threat will
be compared and contrasted with exposure to trimethylthiazoline (TMT), a component of fox odor, representing
the naturalistic but exteroceptive (external) threat of a predator. Responses will be analyzed both in a naïve
state and after animals are exposed to a traumatic, chronic social defeat stress (CSDS).
 Dr. Chan will also dedicate time to the clinical care of veterans. Being dual-trained in internal medicine and
psychiatry, he is particularly suited to treating the complex comorbid conditions often seen in veterans. He will
work on the inpatient psychiatric unit and the psychiatric consult-liaison service at the Iowa City VA Medical
Center.
Methods: Custom electrodes will be constructed and stereotactically implanted into multiple mouse brain sites.
After recovery from surgery, awake, behaving mice will be exposed to threatening stimuli while neural
recordings are performed. Aim 1 will study the effects of CO2 and TMT in naïve animals, with follow-up
exposures after animals have undergone CSDS. Behaviors will be matched against neural signals. Neural
signals will be evaluated for local field potential (LFP) power, firing rates of individual neurons, and for
functional connectivity measures between brain sites. In addition, the bispectral & electome methods will be
used to detect salient neurophysiological features that predict behaviors. Aim 2 will use optogenetic
manipulation of neural signals to modify defensive behaviors. To facilitate these studies, Dr. Chan will take
coursework in automated behavioral scoring and stati...

## Key facts

- **NIH application ID:** 10798625
- **Project number:** 1IK2BX006118-01A2
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Aubrey C Chan
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798625

## Citation

> US National Institutes of Health, RePORTER application 10798625, Identification of Brain Circuits Underlying Fear and Panic (1IK2BX006118-01A2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10798625. Licensed CC0.

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