# Neural circuits regulating flight and panic behavior.

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $444,752

## Abstract

PROJECT SUMMARY
Emotional behaviors, such as defensive responses to threat, are often dysregulated in mental
illness. Currently, there is a poor understanding of the neural mechanisms that control transitions
between modes and magnitudes of defensive responding. Obtaining such knowledge will provide
significant progress toward the long-term goal of providing foundational knowledge used for the
development of better therapeutics for mental illness. The overall objective of this application is
to identify how distributed neuronal circuits control transitions to active forms of defensive behav-
ior. The central hypothesis is that a widespread brain network that includes the central amygdala
(CEA), ventromedial hypothalamus (VMH), periaqueductal grey (PAG), insular cortex (IC), and
ventral hippocampus (vHIPP) controls defensive response transitions. The rationale that under-
lies this proposal is that an enhanced understanding of these complex behavioral states and cir-
cuits will provide foundational data for understanding multiple psychiatric disorders and their
comorbidity. The proposed research tests the central hypothesis with three specific aims: 1) Iden-
tify the functional role of specific projection pathways in defensive action selection; 2) Determine
the impact of structures afferent to the CEA on flight behavior; and 3) Define the neuronal activity
patterns that encode shifts in defensive states from freezing to flight to panic. The first aim will
use viral vector delivery strategies and optogenetics to target and manipulate specific output path-
ways of the CEA. The second aim will use retrograde targeting strategies to manipulate afferents
to the CEA. Finally, the third aim will use deep-brain calcium imaging to monitor neural activity
patterns in specific populations of projection neurons while mice transition through escalating lev-
els of defensive responding. Successful completion of the proposed research will define mecha-
nisms by which widespread brain networks mediate switching to active modes of defensive be-
havior. The proposed research is innovative because it substantially departs from the status quo
by investigating how the brain coordinates transitions between defensive behaviors. This will be
significant because it will lay a foundation that facilitates understanding of the neuronal circuit
basis of the maladaptive responses associated with mental illness. Indeed, this novel systems
neuroscience approach to understanding how fear states are encoded will open new avenues of
research into the neurobiological underpinnings of anxiety- and trauma-related mental health dis-
orders, such as posttraumatic stress and panic disorder.

## Key facts

- **NIH application ID:** 10114335
- **Project number:** 5R01MH122561-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Jonathan P Fadok
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $444,752
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114335

## Citation

> US National Institutes of Health, RePORTER application 10114335, Neural circuits regulating flight and panic behavior. (5R01MH122561-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10114335. Licensed CC0.

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