# Dynamics of activity-induced transcription in single dentate granule cells

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $485,000

## Abstract

Project Summary
For neural networks to be refined and shaped by experience, the expression of new genes in response to
activity is critical. Neural activity triggers the expression of immediate early genes (IEGs) such as arc, fos, and
egr1 within minutes, but many IEGs are transcription factors that in turn trigger subsequent waves of
transcription. These later waves of transcription are necessary for the consolidation of stable, persistent
memories, yet identity and function of the genes in these later waves remains unknown. Further, it is unknown
if all activated neurons in a circuit are identically modulated, or if cell-specific transcriptional changes can drive
emerging functional differences. The extent of this heterogeneity at the level of the individual neuron has been
completely unexplored. Only now, with recent advances in single-cell sequencing technologies, is it possible to
track gene expression changes in individual activated neurons. This project will track activity-related gene
changes in single neurons of the hippocampal dentate gyrus, a region critical for learning and memory,
providing for the first time a transcriptional `signature' of the activity in individual neurons. This will be achieved
by examining dentate granule cells in three aims; First, the long-term waves of transcription will be
characterized during the full time span during which transcription and translation inhibitors have been
demonstrated to impair memory. Second, the impact of each transcriptional wave will be explored in terms of
changes in cell excitability and the probability of activation to a subsequent event either in vivo or in vitro.
Finally, the dentate gyrus is one of the few brain regions that incorporates new neurons during adulthood in
mammals. Immature dentate granule cells are highly similar to their mature counterparts, except that they
possess distinct electrophysiological properties which help to control function across the entire dentate gyrus.
Therefore activity-related transcription of this unique population of immature cells will be characterized, as well
as their functional and transcriptional impact on mature cells. Findings from this project will reveal novel links
between gene expression and function in individual neurons, identifying novel targets for the maintenance of
memory in healthy humans and in restoring memory function in aging or disease states.

## Key facts

- **NIH application ID:** 10191046
- **Project number:** 5R01MH114030-05
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** FRED H GAGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $485,000
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191046

## Citation

> US National Institutes of Health, RePORTER application 10191046, Dynamics of activity-induced transcription in single dentate granule cells (5R01MH114030-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10191046. Licensed CC0.

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