# Neural circuit mechanisms for experience-dependent observational fear

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $493,581

## Abstract

PROJECT SUMMARY
The ability to vicariously experience the other's aversive feelings in a situation, a process called observational
fear (OF), is critical to live in society. Malfunctions of OF represent well-described findings in individuals with
autism spectrum disorders. In OF, an observer witnesses a demonstrator in an aversive situation and
responds with fear behaviors. If the demonstrator's reaction is robust, the observer easily expresses OF
without prior similar experience and social familiarity with demonstrator (we refer to as innate OF). However,
in nature and our lives, the demonstrator's reaction is often ambiguous and thus difficult for the observer to
understand. To fully understand the other's situation, the observer utilizes both prior similar own experience
and social familiarity that facilitate OF (we refer to as experience-dependent OF; Exp OF). While innate OF
primarily depends on the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), the neural
mechanisms of Exp OF remain unexplored. My goal is to elucidate the neural mechanisms of how both prior
similar own experience and social familiarity enable the observer to fully understand the other's aversive
situation from their ambiguous reaction, by examining hippocampal (HPC)-BLA neural circuits in a mouse OF
model that delivers strong electrical shocks to the demonstrator eliciting a robust reaction or weak electrical
shocks eliciting an ambiguous reaction.
 Recently, our preliminary studies showed that ACC is dispensable for Exp OF, while ACC is essential
for innate OF. On the other hand, both dorsal HPC (dHPC) and ventral HPC (vHPC) are crucial for Exp OF,
but not for innate OF. BLA is required for both Exp and innate OF. These findings lead us to propose distinct
neural circuits in Exp and innate OF. The central hypothesis of this model is that the dorsoventral HPC to BLA
pathways generate and reactivate a neural ensemble of BLA neurons encoding prior similar own fear
Guided by strong
preliminary data, first, we propose that the dorsoventral HPC to BLA pathways are crucial for Exp OF, while
the ACC to BLA pathway is essential for innate OF. Second, we propose that the reactivation of a neural
ensemble of BLA neurons encoding prior similar own fear experience (a fear memory ensemble) mediates
Exp OF as the perception-action mechanisms. Third, we propose that the pathway from dHPC to BLA
generates the fear memory ensemble in BLA during own fear experience and then vHPC neurons respond to
the familiar demonstrator's fearful situation to reactivate the fear memory ensemble in BLA to elicit Exp OF.
experience, which facilitates Exp OF, while ACC induces robust BLA activity for innate OF.
 Collectively, our proposed research will broadly impact the field of learning and memory by
characterizing neural circuits and their neural process about how we understand the other's aversive
situational experience. Potentially, the neural mechanisms can be generalized for other typ...

## Key facts

- **NIH application ID:** 10480879
- **Project number:** 5R01MH125916-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Takashi Kitamura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $493,581
- **Award type:** 5
- **Project period:** 2021-09-07 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480879

## Citation

> US National Institutes of Health, RePORTER application 10480879, Neural circuit mechanisms for experience-dependent observational fear (5R01MH125916-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10480879. Licensed CC0.

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