# Hippocampal Mechanisms of Fear Extinction

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $384,809

## Abstract

Project Summary:
The primary clinical treatment for maladaptive fear is extinction—repeated exposure to a fearful stimulus in the
absence of threat. Extinction does not permanently eliminate maladaptive fear. Extinguished fear resurfaces
with the passage of time or if a new trauma is experienced. The transience of extinction suggests that it does
not erase learned fear but, instead, establishes a new memory that competes with the fear memory for
expression. To understand why fear returns, we must know more about the mechanisms controlling the
retrieval or expression of extinction. Here we propose a highly novel approach to elucidate these mechanisms.
Our proposal focuses on the dentate gyrus (DG), a region of the hippocampus that plays a critical role in
acquisition of context fear memory—fear of a place in which an aversive experience occurred. We recently
discovered that DG neural activity is also required for context fear extinction. Under this award, we will use
using activity-dependent neural tagging, a technique that allows us to tag (and later manipulate) neural
ensembles that are active during a behavioral experience, to investigate how neural ensembles in DG
orchestrate the expression of fear and extinction memories. Our central hypothesis is that extinction causes
DG to generate a new context representation, and activation of this extinction representation suppresses fear.
Consistent with this hypothesis, our preliminary studies indicate (1) that fear learning and fear extinction
activate distinct ensembles of “fear neurons” and “extinction neurons” in DG in mice, and (2) the activity of
these ensembles modulates expression of fear and extinction. The proposed studies will leverage these
findings to (1) test the hypothesis that the recovery of fear after extinction reflects changes in the activity of DG
fear and extinction ensembles, (2) identify mechanisms through which these ensembles modulate fear, and (3)
visualize the processing of fear and extinction memory in real-time using in vivo imaging with head-mounted
miniature microscopes. We anticipate that the proposed research will uncover mechanisms controlling the
expression of fear and extinction, reveal why fear recovers after extinction, and identify strategies for making
extinction more durable.

## Key facts

- **NIH application ID:** 10087426
- **Project number:** 5R01MH117426-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** MICHAEL R DREW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,809
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087426

## Citation

> US National Institutes of Health, RePORTER application 10087426, Hippocampal Mechanisms of Fear Extinction (5R01MH117426-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10087426. Licensed CC0.

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