# Activity-Dependent Cellular and Molecular Events Regulating Memory

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $387,500

## Abstract

Activity-dependent Cellular and Molecular Events Regulating Memory
Project Summary
Activity-regulated signaling pathways, by transmitting information regarding synaptic inputs to the nucleus and
regulating gene transcription, play a vital role in memory. Knowing these processes would benefit the
approaches to improve memory. Still, our understanding of the molecular mechanisms that mediate synapse-
to-nucleus signaling remains surprisingly incomplete. In particular, details of how synaptically localized
transcriptional modulators are transported to the nucleus, activate the transcriptional machinery, their target
genes and the neural circuits they serve on are too poorly understood to be harnessed for therapeutic
applications. We propose to address this knowledge gap from a new angle that features a behavioral paradigm
with various training strength, mutants that activate or inhibit gene transcription, epigenetic analysis, and gene
screening. We have developed a training model in the mouse that uniquely positions us to address three aims
that together will markedly advance understanding of the fundamental biology of learning-dependent
intracellular signaling.
Aim 1 will: a) test the molecular mechanism of learning-dependent synapse-to-nucleus transport in the
hippocampus following various strength of training, and b) address potential requirements for transcriptional
activity using mutants that inhibit or activate transcription. Accomplishment of the proposed work will define the
signaling pathways that mediate training responses in gene transcription, establishing the mechanistic
framework for analysis of molecular and cellular changes following various strength of training, and contributing
an overview of signaling pathway requirements in various memory paradigms that are dependent on the
hippocampus.
Aim 2 will define the impact of binding between transcriptional activators and changes in histone modifications
in response to various strength of training and various transcriptional mutants while addressing the overall
hypothesis that epigenetic modifications reflect the transcriptional machinery specific to their corresponding
anatomic circuits. We will conduct a detailed analysis of binding between transcriptional cofactors depending
on their posttranslational modifications. We will use mutant transcriptional inhibitors and activators to define
their role in epigenetic modifications.
Aim 3 will characterize specific gene targets of inducible transcriptional coactivators, epigenetic changes on
their specific promoters following training with various strength and analyze how these changes affected by
mutant transcriptional inhibitors and activators. We will examine in detail the role of these novel gene targets in
memory and in particular in enhancement of memory strength.
Given unequivocal evidence that memory strength is critical for healthy maintenance, molecular and neural
circuitry dissection of learning-dependent mechanisms connecting syna...

## Key facts

- **NIH application ID:** 9989896
- **Project number:** 5R01MH107555-05
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** GLEB P SHUMYATSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2016-09-23 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989896

## Citation

> US National Institutes of Health, RePORTER application 9989896, Activity-Dependent Cellular and Molecular Events Regulating Memory (5R01MH107555-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989896. Licensed CC0.

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