# Disinhibition-assisted LTP as a method for testing role of neuronal circuits in behavior

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $200,365

## Abstract

Project Summary
During development, learning or progression towards disease, the brain undergoes plastic
changes characterized by gradual increases or decreases in synaptic transmission. Modeling
such changes by artificial means is necessary for understanding their functional role. Recently
developed optogenetic and chemogenetic techniques allow neuronal activation or suppression,
but they act in the all-or-none manner and do not allow modeling of gradual synaptic changes.
Meanwhile, such gradual changes can be obtained by inducing long-term potentiation (LTP) or
depression, but these techniques do not work reliably in all areas of the brain, particularly in the
areas with a strong inhibitory control, which include the basolateral amygdala. In the pilot
experiments, we found that a transient chemogenetic or optogenetic suppression of the
somatostatin- but not parvalbumin-positive interneurons enables LTP induction in the prefrontal-
amygdala pathway. Based on these findings and published data, we hypothesize that a transient
suppression of certain classes of the local GABAergic neurons, combined with stimulation of
synapses of interest, will provide a universal means for inducing LTP in the remote inputs to the
local principal neurons in vivo. We will test this hypothesis in Aim 1 using the prefrontal-amygdala
circuit, because its artificial synaptic modulation has been especially difficult to achieve, while
the need for such modulation is high given the role of this circuit in the behavioral traits relevant
to mental disease. In Aim 2, we will test predictions that synaptic efficacy in the dmPFC-BLA
loop determines oscillatory synchronization between the two structures and influences anxiety-
like behaviors. These predictions are based on findings that theta oscillations synchrony
between BLA and dmPFC increase with innate anxiety in the open field, and photostimulation of
BLA axonal terminals in dmPFC acutely increase anxiety-like behaviors in the elevated plus
maze and open field. The study is expected to produce techniques for obtaining LTP of a
desirable magnitude in glutamatergic synapses connecting principal neurons of dmPFC and
BLA. The classes of GABAergic neurons that gate LTP in these pathways will be identified, and
methods for their transient suppression to aid LTP induction will be developed. This LTP
optimization process will provide a template for developing analogous LTP protocols for other
brain areas. The role of synaptic efficacy of the dmPFC-BLA reciprocal projections in oscillatory
synchronization and anxiety-relevant traits will be determined, which will inform about potential
methods for targeted manipulation of that pathway in emotional disorders.

## Key facts

- **NIH application ID:** 9828105
- **Project number:** 5R21MH118604-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Alexei Morozov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,365
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828105

## Citation

> US National Institutes of Health, RePORTER application 9828105, Disinhibition-assisted LTP as a method for testing role of neuronal circuits in behavior (5R21MH118604-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9828105. Licensed CC0.

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