# Cortico-Hippocampal Mechanisms of Context Memory

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $72,902

## Abstract

SUMMARY
 The highest cognitive functions such as reasoning, planning, and decision-making, are all,
directly or indirectly, influenced by our past personal experiences, which are represented in
hippocampal-cortical circuits as episodic memories. Dysfunction of these circuits has been
linked to the most prevalent and challenging mental disorders of our time, ranging from
dementia to anxiety, depression, and post-traumatic stress disorder. Understanding the
neurobiological mechanisms of episodic memory formation and retrieval are therefore essential
for the development of effective molecular and circuit-based therapies for such disorders. We
posit a key role of activity-dependent inflammatory signaling in discrete dorsohippocampal
(DH) projections to the retrosplenial cortex (RSC) DH-RSC circuit in the stabilization and
persistence of stress-related memories. Aim 1 is designed to determine the contributions of
discrete DH-RSC projections to early tagging of RSC and sustained inflammatory signaling in
DH and RSC. Aim 2 will focus on the direct contribution of hippocampal Toll-like receptors (Tlr)
to memory consolidation and induction of TGFb1 and Aim 3 will examine the contribution of
TGFb to the cortical dependence of memories and deactivation of inflammatory signaling in the
DH-RSC circuit. These aims will be tested in mouse models of episodic-like memories by
applying projection-specific manipulations of the DH-RSC circuit, cell-specific genetic
manipulations of Tlr9 and TGFb receptors, and quantitative molecular biologic and imaging
approaches to monitor inflammatory signaling in memory circuits. We hope that circuit specific
Tlr9/ TGFb signaling will emerge as candidate target for therapies for neuropsychiatric
disorders rooted in episodic memory deficits.
 In this supplement, we propose to add Kendra Parker as a member in our project to study
the role of Tlr9 in memory-related inflammatory signaling. Kendra Parker has defined her
career goal explicitly as a future physician scientist. Our goal during her participation in this R01
project is to provide the training in research resulting in publications, and thus ensure that she
receives a strong foundation toward that outcome. We welcome the opportunity to train an
African American woman as a future leader in biological psychiatry, and in the field of
neurobiology of memory in particular.

## Key facts

- **NIH application ID:** 10595966
- **Project number:** 3R01MH108837-08S1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Jelena Radulovic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,902
- **Award type:** 3
- **Project period:** 2016-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595966

## Citation

> US National Institutes of Health, RePORTER application 10595966, Cortico-Hippocampal Mechanisms of Context Memory (3R01MH108837-08S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10595966. Licensed CC0.

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