# Transcriptional control of synaptic plasticity by class IIa HDACs

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $706,569

## Abstract

The goal of this project is to elucidate the molecular mechanisms of experience-dependent plasticity of neural
circuits essential for learning and memory. We focus on class IIa histone deacetylases (HDACs), transcriptional
repressors that shuttle between the nucleus and cytoplasm. We and our colleagues have previously
demonstrated that the class IIa HDAC isoform, HDAC4, regulates memory in mice, drosophila and C.elegans.
In conjunction with these findings, HDAC4 has been linked to several neurological disorders in humans. In the
initial project period, we discovered that HDAC4 and its close homolog, HDAC5, restrict the transcriptional
response to sensory input. These observations support the hypothesis that plasticity- and memory-related genes
are dynamically repressed in the brain in any environment. Here, we propose to determine how class IIa HDACs
operate at circuit, cellular and molecular levels, and how their nuclear signaling impacts neurons in the mouse
hippocampus. Moreover, we will exploit class II HDACs as tools for rapid chemical-genetic control of transcription
in behaving animals.
Our aims are: 1) To determine how class IIa HDAC operate at a circuit level by using immunofluorescent
microscopy, activity-based tagging of memory engrams cells, and in vivo 2-photon imaging of repressors and
calcium indicators; 2) To identify nuclear effectors of class IIa HDACs in specific genetically-defined neuron types
by deep sequencing and mass spectrometry; 3) To define the consequences of class IIa HDACs signaling on
circuit structure and function. This will be accomplished by combining electron microscopy, whole-brain imaging,
and electrophysiology; and 4) To leverage chemical-genetic manipulation of class IIa HDAC signaling for
mapping of brain areas where activity-dependent transcription promotes memory coding.
Taken together, these studies will explain how neuronal chromatin-binding proteins associated with human
disease function in the normal brain, and will provide novel insights into the basic mechanisms underlying
network plasticity and memory storage.

## Key facts

- **NIH application ID:** 10117286
- **Project number:** 5R01NS087026-06
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Anton Maximov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $706,569
- **Award type:** 5
- **Project period:** 2014-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117286

## Citation

> US National Institutes of Health, RePORTER application 10117286, Transcriptional control of synaptic plasticity by class IIa HDACs (5R01NS087026-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10117286. Licensed CC0.

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