# Hippocampal adult-born neurons in social memory circuits

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $587,742

## Abstract

PROJECT SUMMARY
Severe social impairment is a shared symptom of many neuropsychiatric illnesses. In particular, deficits in the
ability to recognize and remember previously encountered individuals—often called social memory—can
significantly compromise an individual’s ability to form and maintain social relationships, dramatically reducing
quality of life. Among the brain regions associated with social impairment, the hippocampus is notable due to its
essential role in social memory and its exceptional structural plasticity, including the continuous generation of
new neurons in the dentate gyrus throughout adulthood. Harnessing naturally occurring structural plasticity in
the hippocampus may be a valuable approach for stimulating neural circuits and restoring social memory
function. Thus, the goal of this R01 proposal is to uncover the contribution of hippocampal structural plasticity to
social memory circuits. Our published work demonstrated that adult-born neurons in the dentate gyrus are
necessary for consolidating and/recalling social memories for conspecifics. Yet, the extent to which adult-born
neurons are recruited to social memory traces and contribute selectively to social memory processes is
undetermined. Adult-born neurons form multiple cellular connections within the hippocampus, including with CA2
neurons. While largely understudied, the CA2 region of the hippocampus has emerged as a critical hub for social
memory function. We do not know whether adult-born neurons influence social memory circuits and function via
their connections with CA2. In our preliminary studies using a mouse model of social dysfunction, the Shank3B
KO mouse, we found impaired social memory along with hippocampal aberrations, including fewer adult-born
neurons and diminished afferents from adult-born neurons to CA2 compared to wild-type littermates. We then
used chemogenetics to activate CA2 neurons and the CA2-to-ventral CA1 pathway and were able to rescue
social memory dysfunction in Shank3B KO mice, suggesting this circuitry as a pivotal intervention point for
improving function. Here, we propose to use transgenic, chemogenetic, and pharmacologic manipulations
combined with behavioral, histological, and in vivo electrophysiological analyses to test the hypothesis that
afferent innervation of CA2 by adult-born neurons is critical in regulating social memory function, and
that targeting this circuitry can alleviate social memory dysfunction. Specifically, we will elucidate the
preferential recruitment of adult-born neurons to social memory engrams and their selective contribution to social
memory function (Aim 1), identify the influence of adult-born neuron afferents to CA2 on CA2 oscillatory activity
and social memory function (Aim 2), and explore enhancing hippocampal adult-born neuron circuitry to improve
social memory deficits in Shank3B KO mouse (Aim 3). These studies will provide a mechanistic understanding
of how adult-born neurons impact social memory ...

## Key facts

- **NIH application ID:** 10870009
- **Project number:** 5R01MH133744-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Elise C Cope
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $587,742
- **Award type:** 5
- **Project period:** 2023-06-16 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870009

## Citation

> US National Institutes of Health, RePORTER application 10870009, Hippocampal adult-born neurons in social memory circuits (5R01MH133744-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870009. Licensed CC0.

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