# How Fear Learning Alters Sensory Representations of Threat Predictive Stimuli

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $507,222

## Abstract

Threatening or aversive stimuli normally evoke healthy fear, in which the brain’s defensive motivational systems
drive protective behaviors. When a person or animal learns that a particular sensory stimulus predicts future
harm, that stimulus begins to evoke fearful reactions as well. This is called learned fear. Sensory stimuli that are
physically similar or conceptually related to the threat-predictive stimulus normally also evoke fear because of
the reasonable belief that they might also predict future harm. This is called generalization of learned fear, and
it is a normal part of healthy fear. However, many Americans suffer from disordered fear, in which the feeling of
acute threat (fear) or potential threat (anxiety) generalizes to inappropriate stimuli and situations that may
resemble or be associated with traumatic events but do not actually indicate an impending threat. Figuring out
how to limit generalization so that a patient is only fearful in appropriate situations is a key practical challenge
for the treatment of anxiety disorders. Most research on the biological basis of anxiety disorders and learned
fear has focused on the mechanisms by which the brain learns the initial fear and extrapolates fearful behavior
across situations. However, evidence is accumulating that learned fear also evokes profound changes in the
brain’s sensory systems. This includes becoming hyper-sensitive and hyper-responsive to threat-predictive
stimuli in ways that may underlie common post-traumatic symptoms like hyper-vigilance and attentional bias
toward threat-predictive stimuli. In the previous project period we used a mouse model to observe how the
neurobiology of the olfactory system is changed during appropriate fear and observed that fear learning makes
the olfactory system selectively hyper-responsive to threat-predictive odor, generating a neural “alarm signal” as
early as the sensory input to the brain. In contrast, in this project period we will explore the more clinically-
relevant situation of fear generalization, where initial trauma evokes fear of new stimuli that may not actually
predict a threat. In preliminary experiments we employed an experimental paradigm in which mice undergo a
traumatic experience associated with a particular odor but then generalize their fear across many novel odors.
We will test whether this experience causes the olfactory system to become non-selectively hyper-responsive to
many dissimilar odors, which might drive downstream responding as if the new odors are dangerous. We will
also investigate the neural circuitry by which information about the traumatic event reaches the olfactory system
and induces change in the response to many different odors. Finally, we will evaluate multiple candidate
approaches to reverse the behavioral and sensory consequences of fear generalization, including comparing
conventional exposure (a.k.a. extinction) therapy using the original trauma-associated odor with new therapy
paradigms ...

## Key facts

- **NIH application ID:** 10312005
- **Project number:** 5R01MH101293-09
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** John P McGann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $507,222
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312005

## Citation

> US National Institutes of Health, RePORTER application 10312005, How Fear Learning Alters Sensory Representations of Threat Predictive Stimuli (5R01MH101293-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312005. Licensed CC0.

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