# Endocannabinoid regulation of ventral hippocampus-nucleus accumbens circuit and consequences for stress-mediated behaviors

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $31,990

## Abstract

Summary: Post-traumatic stress disorder and other anxiety disorders are the most common mental illnesses
in the United States, affecting nearly one third of Americans at some point in their life. However, this growing
public health concern is met with limited efficacious pharmacotherapies despite billions of dollars invested in
drug development. Research has begun to focus on the neural processes mediating stress susceptibility as a
potential target for therapeutics; as such, the endocannabinoid system has recently emerged as a central
regulator of stress responsivity, avoidance behaviors, fear generalization, and aversive learning processes, and
is thus a compelling candidate for future drug development. Augmentation of endocannabinoid signaling has
been shown to reduce stress-induced avoidance and promote stress resilience. Here, we aim to understand
which neural circuits drive endocannabinoid-mediated protection of deleterious stress effects. Recent evidence
has implicated the ventral hippocampus (vHIPP)-nucleus accumbens (NAc) circuit in mediating stress
susceptibility, and we have collected data confirming that endocannabinoids regulate vHIPP-NAc synapses. In
this proposal, we will combine approach/avoidance behavioral paradigms, with optical tools for recording (fiber
photometry) and manipulating (INTERSECT viral approach) endocannabinoid signaling to elucidate the role of
circuit-specific endocannabinoid signaling in mediating stress adaptations. Together, this proposal will give me
the technical and theoretical training to answer complex questions about the neural basis of behavior and its
dysregulation in stress-induced disorders. In Aim 1, I will characterize what sort of stimuli induce
endocannabinoid release in vivo at vHIPP-NAc synapses using a novel endocannabinoid sensor in conjunction
with fiber photometry. These studies allow for temporal dynamics and activity-dependent mechanism mediating
stress-induced endocannabinoid release, in vivo, for the first time. In Aim 2, I will define cell-type specific
endocannabinoid regulation of vHIPP-NAc circuitry using whole cell patch clamp electrophysiology and
transgenic reporter mice to identify discrete neuronal populations; this will provide cell-type specific assessment
of how endocannabinoids mediate neural activity in the NAc. Finally, in Aim 3, I will selectively delete components
of the endocannabinoid system from vHIPP-NAc circuit. This will allow us to define the sufficiency and necessity
of endocannabinoid signaling in various aspects of stress-responsive avoidance behaviors. Through these novel
findings, we will learn about the mechanisms that mediate dysfunctional stress responding and how the
endocannabinoid system may present a therapeutic target to develop more specific drugs to treat psychiatric
disorders.

## Key facts

- **NIH application ID:** 10386602
- **Project number:** 1F31MH126460-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Veronika Kondev
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,990
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386602

## Citation

> US National Institutes of Health, RePORTER application 10386602, Endocannabinoid regulation of ventral hippocampus-nucleus accumbens circuit and consequences for stress-mediated behaviors (1F31MH126460-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10386602. Licensed CC0.

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