# Local translation mechanisms to control inhibitory synaptic plasticity

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $490,551

## Abstract

Project Summary
Synaptic inhibition in the brain is mostly mediated by GABAergic inhibitory synapses, which are essential in
controlling neuronal firing, neuron and circuit excitability, and synaptic plasticity. Inhibitory synapses undergo
multiple modes of plasticity but the molecular mechanisms that drive persistent inhibitory post-synaptic plasticity
remain poorly defined. As translation of synaptic proteins is essential for many forms of plasticity, synthesis of
new inhibitory post-synaptic proteins likely plays a key role in sustaining changes in inhibitory synaptic strength.
However, little is known about which inhibitory synaptic proteins are translated, where they are produced and
how this process is regulated during activity. Our preliminary work suggests that multiple inhibitory synaptic
proteins are locally translated in neuronal dendrites during inhibitory long-term potentiation. This process is tightly
regulated by miRNAs, potent negative-regulators of translation. This proposal will examine the control of
inhibitory synaptic plasticity by local miRNA-dependent translational regulation, using in vivo and in vitro
advanced imaging and electrophysiological approaches. The proposed studies are significant as they have the
potential to reveal key mechanisms that drive persistent and long-lasting changes in synaptic inhibition. Given
the important roles of inhibitory synapses in the brain, this project will provide crucial insight into the underlying
mechanisms of learning, memory and cognition.

## Key facts

- **NIH application ID:** 10517897
- **Project number:** 1R01MH128199-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Katharine Rachel Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $490,551
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10517897

## Citation

> US National Institutes of Health, RePORTER application 10517897, Local translation mechanisms to control inhibitory synaptic plasticity (1R01MH128199-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10517897. Licensed CC0.

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