# Hippocampal modulation of subcortical circuits in the control of emotional behavior

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $660,467

## Abstract

Project Summary
Almost a third of adult Americans suffer from an anxiety disorder, carrying an enormous
personal, societal and financial burden. Anxiety disorders are complex circuit-based conditions,
resulting from dysfunction in a number of distributed regions, connections, and cell types that
generate normal adaptive behavior. Thus, a deeper understanding of how these neural circuits
become disrupted to generate maladaptive behavior is crucial if we hope to generate new
treatments. In recent years, we have shown that the ventral hippocampus (vHPC) is an central
node in the extended circuit that generates adaptive avoidance behavior. However, the input-
output organization of the ventral hippocampus in the control of anxiety-related behavior
remains poorly understood. Here, we will use functional imaging of large populations of
anatomically defined vHPC neurons, optical manipulation of these neurons, and high resolution
behavioral analyses to expand our understanding of how the extended ventral hippocampal
network controls behavior. We will first determine the encoding properties of vHPC output
neurons to subcortical areas known to drive avoidance and anxiety-like behavior. Then, we will
adopt new unsupervised behavioral classification tools for understanding anxiety-related
behavior in mice to determine how vHPC projection neurons orchestrate distinct behavioral
states. Finally, we will determine how distinct inputs to the differentially modulate avoidance
behavior and shape anxiety-related representations in vHPC. This will provide the most detailed
functional map of the extended hippocampal circuit that controls avoidance behavior, and
provide novel targets for generation of therapeutics for the treatment of anxiety disorders.

## Key facts

- **NIH application ID:** 10211484
- **Project number:** 2R01MH108623-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Mazen A Kheirbek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $660,467
- **Award type:** 2
- **Project period:** 2016-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211484

## Citation

> US National Institutes of Health, RePORTER application 10211484, Hippocampal modulation of subcortical circuits in the control of emotional behavior (2R01MH108623-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10211484. Licensed CC0.

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