# Contextual Fear Differentiation, Sex Differences and Acetylcholine

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $368,325

## Abstract

Fear in nonthreatening contexts is a hallmark of anxiety disorders. The hippocampus' plays a critical role in
recognizing a context as a previously experienced dangerous one or a safe one. We will study the ability to
differentiate such contexts in rats. Rats have proven to be an excellent model of human anxiety disorders. Rats
need a period to explore a context in order to learn that it is dangerous. Our data indicate that a period just
long enough to support robust fear learning results in generalizing that fear to any similar context. They need a
longer period to learn a specific fear that allows them to distinguish between danger and safety. We will study
the biology of this type of learning. We will examine how a particular neuromodulator, acetylcholine (ACh),
influences the ability for this learning and have discovered that stimulating this neuromodulatory system
enhances the learning. Anxiety disorders are much more prevalent in women and we will test the hypothesis
that at certain times during the female cycle, when metabolites of progesterone are high, they act to dampen
the brain's response to this neuromodulator. This results in a state where fear learning will be more
nonspecific and generalize to safe situations. To study this we will use optogenetics to selectively stimulate
ACh and measure release of this neuromodulator with a novel biosensor implanted in a brain region
responsible for learning. We will also measure the rhythms of brain activity produced by the neuromodulator,
the ability to learn fear and to differentiate safe and dangerous environments. We will compare male and
female rats and also compare females in different stages of their cycle. This will provide a deeper
understanding of why anxiety disorders develop and why they are more prevalent in women.

## Key facts

- **NIH application ID:** 9851432
- **Project number:** 5R01MH062122-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Michael S Fanselow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,325
- **Award type:** 5
- **Project period:** 2001-09-16 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851432

## Citation

> US National Institutes of Health, RePORTER application 9851432, Contextual Fear Differentiation, Sex Differences and Acetylcholine (5R01MH062122-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9851432. Licensed CC0.

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