# Odor-Reward Association Encoding in CA2 and its Contribution to Social Memory

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

PROJECT SUMMARY
 Impairments in social memories are central to many neuropsychiatric disorders, including Schizophrenia
(SZD). This application investigates olfactory processing in the CA2 region of the rodent hippocampus and its
contribution to social memory—the ability to encode and recall another conspecific. CA2 is necessary for social
memory in rodents; inhibiting dorsal CA2 (dCA2) during an initial social interaction disrupts a mouse’s ability to
form and recall that social memory. But how CA2 precisely contributes to encoding and retrieval remains unclear.
Since mice rely on olfaction to investigate social targets, I hypothesize that murine CA2 is vital to the integration
and discrimination of social olfactory cues that provide valent information about different conspecifics. In a pilot
study using water-restricted female mice, I found that silencing CA2 activity with inhibitory opsins showed a trend
towards impairing the mice’s abilities to distinguish one male mouse urine from another in a head-fixed, Go/No-
Go Odor Discrimination Task, in which GO odors are paired with a water reward. Using 2-photon calcium imaging
in seven mice, a collaborator and I have discovered that dCA2 processes both social and nonsocial odors.
Moving forward, I am using 2-photon imaging to test how CA2 uses olfactory information to discriminate between
odor stimuli and to associate odors with conditioned or unconditioned valences, and how perturbation of this
processing affects social memory in disease. In Aim 1, I am identifying sex differences, if any, in CA2 function
with respect to the encoding of five odors—two naturally valent male urines (social odors), methyl butyrate and
ethyl acetate (nonvalent nonsocial odors), and a mock odor (water)—in a “three-phase paradigm” (TPP) involving
passive odor delivery before and after active odor discrimination. In Aim 2, I will compare the social and nonsocial
odor processing functions of dCA2 and dCA1 (known to process nonsocial odor-reward associations) in the TPP
odor task. I will also train multiple decoders to predict stimulus identity from 2-photon calcium imaging data,
looking for what kinds of stimuli are important to each region (social, nonsocial, rewarded, or nonrewarded odors)
based on decoder performance. Aim 3 examines an SZD genetic mouse model of the human 22q11.2 deletion
syndrome—Df(16)A+/- mice—which shows a profound deficit in social memory. In a second odor discrimination
pilot study, I found that Df(16)A+/- female mice resemble the performance of the CA2-silenced mice in their
impaired ability to distinguish between two social odors. Hence, I will use 2-photon imaging to compare CA2
responses to odor stimuli in this mouse model to that of their neurotypical cagemates. Furthermore, I will attempt
to rescue this social odor discrimination deficit with injection of a TREK-1 dominant-negative virus, which has
been shown to improve neuronal firing in the pathologically hyperpolarized CA2 neurons harbor...

## Key facts

- **NIH application ID:** 10475028
- **Project number:** 5F31MH126622-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Shivani Bigler
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475028

## Citation

> US National Institutes of Health, RePORTER application 10475028, Odor-Reward Association Encoding in CA2 and its Contribution to Social Memory (5F31MH126622-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10475028. Licensed CC0.

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