# Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $400,000

## Abstract

Project summary
Forming stronger aversive memories is a characteristic of PTSD. Meanwhile, psychological
trauma is a risk factor for developing PTSD in the future, upon exposure to another adverse
event. This project will use mice to investigate how observing fear in others, as a form of social
distress, enhances the retention of new inhibitory avoidance (IA) memories. It serves our long-
term goal to understand how neuronal plasticity contributes to emotional behaviors and to
identify the means for reversing PTSD-relevant behavioral traits by artificial circuit
manipulations. We have recently found that a brief exposure to a conspecific receiving electrical
footshocks, the observational fear paradigm (OF), enables a stronger inhibitory avoidance (IA)
learning in mice.
Our preliminary data strongly implicate the pathways between the dorsomedial prefrontal cortex
(dmPFC) and basolateral amygdala (BLA) pathway in the enhancement. First, a
pharmacogenetic disconnection of these structures during OF prevented the enhancement.
Second, OF enabled facilitation of this pathway by IA training, which lasted for several hours.
Third, OF generated NMDAR-only (silent) synapses, which we unsilenced by IA training. In
addition, OF attenuated GABAbR-mediated depression of the feedforward GABAergic currents,
evoked in BLA neurons by a 5 Hz repeated stimulation of the dmPFC inputs. We will test a
hypothesis that OF enhances IA by generating silent synapses and by altering the GABAbR-
dependent inhibitory balance between PV- and Sst-IN in the prefrontal-amygdala circuit, both of
which enable a stronger synaptic facilitation during IA training. We will determine the necessity
of dmPFC-BLA synapses at each phase of the OF-IA paradigm (Aim 1), test the causal role of
the silent synapses and the transient synaptic facilitation (Aim 2), and identify the micro-circuit
mechanism responsible for the abnormally high plasticity (Aim 3). The study may inform about
potential targets and methods for early intervention to prevent PTSD in traumatized people.

## Key facts

- **NIH application ID:** 10159754
- **Project number:** 5R01MH120290-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Alexei Morozov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2019-07-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159754

## Citation

> US National Institutes of Health, RePORTER application 10159754, Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors (5R01MH120290-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159754. Licensed CC0.

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