# Decoding neuronal activity history at the genome through the spatially segregated inducible transcription factors.

> **NIH NIH DP2** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $1,372,500

## Abstract

Project Summary/Abstract:
During learning, task-relevant neurons convert transient activity signals into stable modifications of their synaptic
properties in order to alter their output and support memory formation, a process broadly called plasticity. The
most enduring forms of plasticity require regulation of the genome. Inducible transcription factors (ITFs) are a
subset of rapidly induced, activity-dependent genes that support plasticity by triggering downstream programs
of gene expression that directly impact neuronal functions. Indeed, ITFs have been used as tools to track task-
relevant neurons in vivo during behavior, and intensive efforts in the field have uncovered mechanisms that link
diverse extracellular stimuli and depolarizing activity to ITF expression in neurons. Despite this long-standing
interest in ITFs, a wide gap has emerged in the study of their neuronal functions: What features of neuronal
activity do ITFs communicate to the nucleus? Can they regulate the genome in distinct ways in response to
different forms of activity? Does ITF-mediated gene regulation support synaptic and behavioral adaptations
tailored to the activity history of the cell? Answering these questions requires a shift of the status quo away from
thinking of ITF expression as a generalized response to neuronal activity. This proposal presents the innovative
hypothesis that the genome decodes learning rules to support synaptic plasticity through activity-reporting ITF
expression pathways. This project establishes a discovery pipeline that will reveal genomic mechanisms
underlying neural circuit plasticity by first profiling activity-dependent ITF expression mechanisms in the murine
hippocampus, and then mapping and manipulating ITF target genes to determine their impact on local synapse
functions. The results of this project have the potential to dramatically expand the repertoire of intracellular
signaling and genomic mechanisms available to neurons and other excitable cell types to flexibly update their
functions and phenotypes in response to extracellular stimuli.

## Key facts

- **NIH application ID:** 10244737
- **Project number:** 1DP2NS127276-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Gian-Stefano Brigidi
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,372,500
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244737

## Citation

> US National Institutes of Health, RePORTER application 10244737, Decoding neuronal activity history at the genome through the spatially segregated inducible transcription factors. (1DP2NS127276-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244737. Licensed CC0.

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