# Synaptic and neuronal mechanisms of fear control: the role of hippocampal-amygdalar interactions

> **NIH NIH R01** · MCLEAN HOSPITAL · 2022 · $486,291

## Abstract

Projections from the ventral hippocampus (vHPC) to the amygdala, its basolateral nucleus (BLA), specifically,
play an essential role in context representation in the amygdala during encoding of fear memory extinction.
However, synaptic and network-level mechanisms by which vHPC-amygdala projections may control the function
of the amygdala and amygdala-dependent fear-related behaviors are largely unknown. Combining the use of
chemogenetic and optogenetic techniques with ex vivo and in vivo electrophysiology, tract tracing with viral
vectors and behavioral training and testing, we will explore the functional roles of vHPC-amygdala projections in
conditioned fear and fear extinction at synaptic and circuitry-specific levels. In Aim 1 we will investigate how the
mechanisms of synaptic plasticity in vHPC projections to subnuclei of the amygdala affect the signal flow in
neural circuits of fear conditioning and extinction. Optogeneticaly activating vHPC-amygdala projections, we will
record from neurons in different subdivisions of the amygdala in slices from control, fear-conditioned and fear-
extinguished mice and assay the effects of behavioral training on both excitatory and inhibitory drive in recorded
neurons and their synaptically-driven spike firing output. We will then explore the role of the vHPC-amygdala
pathway in control of fear-related behaviors (Aim 2). Specifically, we will examine the contributions of
behaviorally-induced synaptic plasticity at vHPC inputs to the amygdala, specifically focusing on long-range
GABAergic vHPC-BLA projections (identified by us), to the encoding of context-dependency of fear extinction
memory using chemogenetic tools. We will also systematically explore whether extinction-associated
potentiation of GABAergic synaptic transmission at vHPC-BLA projections may satisfy criteria of synaptic
plasticity and memory (SPM) hypothesis, thus possibly linking these plastic synaptic modifications to the
encoding of context-dependency of fear extinction. Finally (Aim 3), we will investigate the synaptic and neural
circuit-level mechanisms in vHPC-amygdala projections implicated in fear renewal triggered by repeated stress
in fear extinguished mice. We hypothesize that repeated stress may affect the mechanisms of extinction-
triggered synaptic plasticity in vHPC-BLA projections, impairing context representation, and, therefore, possibly
resulting in fear renewal. Our studies could identify specific synaptic mechanisms and neural projections which
could potentially be targeted for therapeutic treatments of disorders implicating dysfunctions of the fear system
of the brain.

## Key facts

- **NIH application ID:** 10378676
- **Project number:** 5R01MH123993-03
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** VADIM BOLSHAKOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $486,291
- **Award type:** 5
- **Project period:** 2020-06-05 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378676

## Citation

> US National Institutes of Health, RePORTER application 10378676, Synaptic and neuronal mechanisms of fear control: the role of hippocampal-amygdalar interactions (5R01MH123993-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10378676. Licensed CC0.

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