# Interrogating Synaptic Mechanisms Underlying Contextual Fear Conditioning Amnesia in Rodent Model of Highly Repetitive Mild Traumatic Brain Injury

> **NIH NIH F30** · GEORGETOWN UNIVERSITY · 2024 · $44,566

## Abstract

Abstract
Traumatic brain injury is the most common neurological disorder and 80% consist of mild traumatic brain injury
(mTBI). The severity and persistence of cognitive symptoms is increased with additional repeat mTBIs (rmTBI).
A high frequency head impact (HF-HI) mouse model of rmTBI developed by the Burns lab displays decreased
learning and changes in transcriptomic profiles related to synaptic signaling accompanied by decreased plasticity
and synaptic changes in CA1 pyramidal neurons. This would suggest that synaptic modifications underly the
anterograde cognitive symptoms following rmTBI. It is still unknown how rmTBI directly effects an already
established memory. Engrams, defined as lasting physical or chemical changes in neurons, are the neural
substrate underlying episodic memory. Studies in transgenic rodents use immediate early genes and
pharmacological labeling, can tag engram cells in contextual fear conditioning (CFC) paradigms. Subsequent
optogenetic reactivation of engrams in the hippocampal formation is sufficient to elicit memory recall outside the
conditioned context and reanimate fear memories in models of amnesia. Preliminary data has shown that the
HF-HI model reduces freezing time in CFC probe trials and engram cells expressing Chr2-YFP can be tagged
in transgenic engram mice. I propose to interrogate immunohistological and electrophysiological properties of
engram cells to explore architectural or synaptic modifications in the repeat head impact brain. I will also use
optogenetics in vivo to reanimate amnestic memories. This research will explore how synaptic modification
relates to retrograde cognitive deficits following rmTBI and probe memory recall, not memory substrate loss, as
a mechanism for retrograde amnesia.

## Key facts

- **NIH application ID:** 10760225
- **Project number:** 5F30NS122281-03
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Daniel Chapman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,566
- **Award type:** 5
- **Project period:** 2022-02-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760225

## Citation

> US National Institutes of Health, RePORTER application 10760225, Interrogating Synaptic Mechanisms Underlying Contextual Fear Conditioning Amnesia in Rodent Model of Highly Repetitive Mild Traumatic Brain Injury (5F30NS122281-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10760225. Licensed CC0.

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