# Contributions of hippocampal oxytocin receptors to social recognition

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $313,550

## Abstract

Project Summary
Prior to neuronal loss in the medial temporal lobe in Alzheimer's disease (AD), there are
numerous pathological changes including alterations in ABeta and tau, inflammation and
microglial functions and neural circuit/synaptic dysfunction that are associated with a mild
cognitive impairment (MCI). fMRI studies have documented hippocampal hyperactivity and
alterations in dentate gyrus (DG)-CA3 dependent functions such as pattern separation-pattern
completion balance in MCI and during aging. Behaviorally, this manifests as episodic (including
social) memory imprecision. At a circuit level, excitation-inhibition (E-I) imbalance in DG-CA3
are associated with these cognitive changes. Furthermore, the antiepileptic drug levetiracetam
has been shown to decrease DG-CA3 hyperactivity and improve cognition in individuals with MCI
and ameliorate E-I imbalance in AD mouse models. Importantly, direct optogenetic stimulation
of parvalbumin basket cells or chemogenetic attenuation of neural activity decreases amyloid load
in multiple mouse models of AD. These observations from human and mouse studies suggest
that decreasing neuronal hyperactivity and recruiting GABAergic inhibition may directly
modulate amyloid plaque burden and memory impairment. Here, we will build on our
preliminary data and will investigate how a molecular factor that promotes recruitment of PV INs,
Ablim3, maybe harnessed to increase feed-forward inhibition in DG-CA3 circuit of the APPNL-F
knock-in mouse model of AD, decrease amyloid load, reduce CA1 hyperactivity, and improve
social memory precision. Together, the proposed Aims will leverage ongoing efforts investigating
how oxytocin receptors in DG-CA3 circuitry modulate social memory precision in the parent
NIMH Ro1 while conveying a new direction that may illuminate the therapeutic potential of
harnessing Ablim3 to dampen hippocampal DG-CA3 hyperactivity, reduce amyloid burden and
improve social memory precision in AD.

## Key facts

- **NIH application ID:** 10286210
- **Project number:** 3R01MH111729-04S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Amar Sahay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,550
- **Award type:** 3
- **Project period:** 2017-11-15 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286210

## Citation

> US National Institutes of Health, RePORTER application 10286210, Contributions of hippocampal oxytocin receptors to social recognition (3R01MH111729-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10286210. Licensed CC0.

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