# Investigating the Role of the Dorsal Hippocampus to Nucleus Accumbens Pathway in Regulating Social Interaction

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $259,500

## Abstract

Abstract
 Major Depressive Disorder (MDD) is a major public health problem across the globe. Despite growing
awareness and treatment, existing antidepressant therapies often leave patients with residual symptoms.
Moreover, some of the most debilitating symptoms of MDD, such as impaired social interaction, lack specific
pharmacologic therapies entirely. Targeting these symptoms could improve outcomes not only in MDD, but
also in other disorders where social interaction is affected, such as Autism Spectrum Disorder.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have recently been identified as a
possible therapeutic target for the treatment of behavioral changes related to chronic stress. These
nonspecific cation channels play a role in regulating neuronal excitability. Antagonizing HCN channels in the
dorsal hippocampus (dHC) promotes excitability and limits behavioral changes in response to chronic stress
in animal models. However, the dHC is mostly known for its role in spatial navigation and early investigators
did not find evidence of projections from the dHC to brain regions involved in the regulation of behaviors that
are affected by chronic stress. As such, it remains unclear why altering dHC excitability through
changes in HCN channel expression would influence animal behavior.
 Recent work has emphasized the role of a projection from the dHC to the nucleus accumbens (NAcc)
in the regulation of motivated behavior to a sucrose reward. Unlike the dHC, activity in the NAcc has
previously been shown to influence social interaction behavior. As a result, we hypothesize that the dHC
to NAcc projection plays an essential role in regulating social interaction and we will investigate this
hypothesis in two aims. In Aim 1, we will perform fiber photometry (FP) in order to study the activity of
projections from the dHC to the NAcc. These experiments will utilize animals subjected to chronic social
defeat (CSD), a chronic stress paradigm that leads to impaired social interaction behavior in a subset of mice
(termed ‘susceptible’ mice). In Aim 2 we will utilize a novel viral approach to enhance cellular excitability in
the dHC to NAcc pathway in order to try and rescue social interaction behavior after CSD in susceptible mice.
We predict that by altering the excitability of the dHC to NAcc pathway, we will be able to rescue the
behavioral changes that occur following CSD. These experiments will help define a new function of the dHC
in health and in response to chronic stress.

## Key facts

- **NIH application ID:** 10195843
- **Project number:** 1R21MH126272-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Dane M Chetkovich
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $259,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195843

## Citation

> US National Institutes of Health, RePORTER application 10195843, Investigating the Role of the Dorsal Hippocampus to Nucleus Accumbens Pathway in Regulating Social Interaction (1R21MH126272-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195843. Licensed CC0.

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