# Hippocampal-cortical neural mechanisms for observational fear in mice

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $67,446

## Abstract

Project Summary/Abstract
Learning and predicting dangerous environments is crucial for individual fitness. Social fear learning is a process
by which individuals can learn about harmful stimuli through observing the aversive situations of other
conspecifics. Observational fear (OF) is a model of social fear learning where an observer witnesses a
demonstrator’s aversive situation and responds by engaging in fear-related behaviors. For example, mice learn
to fear a previously neutral context by watching a demonstrator mouse receive foot-shocks. Humans learn to
fear a previously neutral conditioned stimulus (CS) by watching a demonstrator receive a shock when the CS is
present. For both rodents and primates, OF is enhanced when the observer has prior experience in a similar
aversive context, and when the observer is familiar with the demonstrator. However, the neural mechanisms that
underlie how prior similar experience and social familiarity affect OF are currently unknown. The goal of this
proposal is to investigate the underlying neural mechanisms that explain how prior similar experience and
familiarity with the demonstrator facilitate OF in observers. The dorsal anterior cingulate cortex (ACC) has been
established as an important center for OF. In mice, inhibition of ACC reduces OF, whereas stimulation of ACC
facilitates OF. In humans, ACC activity is associated with enhanced OF. The ability of prior similar experience
and social familiarity to enhance OF suggests that there is also a strong memory system component of OF.
Specifically, dorsal hippocampus (dHPC) is critical for the formation and recall of contextual fear experience,
whereas ventral HPC (vHPC) is critical for social recognition and discrimination. Moreover, afferents from dHPC
through medial entorhinal cortex, and vHPC project to ACC. Thus, interactions between dHPC, vHPC, and ACC
likely facilitate the effects of prior similar experience and social familiarity to enhance OF. This proposal will test
the hypothesis that dHPC activity during prior shock experience contributes to the formation of a fear memory in
ACC of observers that is reactivated during OF testing with a familiar demonstrator, thus enhancing OF. Aim 1
will establish and characterize an OF model that incorporates prior similar experience and social familiarity in
male and female mice. Aim 2 will use chemogenetic methods to inhibit dHPC, vHPC, and ACC in observers
during prior shock experience or during OF with a familiar demonstrator, to determine the necessity of these
brain regions during prior shock experience and during OF testing to enhance OF. Aim 3, will combine
chemogenetics and in vivo calcium imaging to image ACC neuronal activity in observers while dHPC is inhibited
during prior shock experience or while vHPC is inhibited during OF testing with a familiar demonstrator. Together,
the studies in this proposal will advance understanding about the fundamental neural mechanisms of social fear
learning and emp...

## Key facts

- **NIH application ID:** 9991635
- **Project number:** 5F32MH119721-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Joseph Terranova
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991635

## Citation

> US National Institutes of Health, RePORTER application 9991635, Hippocampal-cortical neural mechanisms for observational fear in mice (5F32MH119721-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991635. Licensed CC0.

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