# Molecular and cellular mechanisms underlying activity dependent gene regulation in neurons

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $76,452

## Abstract

Project Abstract/Summary
In neurons, membrane depolarization leads to the expression of immediate early gene
transcription factors (IEG-TFs), including NPAS4, that regulate programs of gene expression
associated with plasticity. IEG-TFs are widely used as tools to identify task-relevant neurons in
vivo, yet it is unclear if these proteins are induced in response to changes in the action potential
(AP) output or synaptic inputs (EPSPs) to the neuron. Even less is known about whether APs
and EPSPs can lead to distinct patterns of gene regulation and cellular phenotypes. This
information “transfer function” is an essential component of how neurons monitor and regulate
their own activity. In the specific case of NPAS4, an IEG-TF that regulates excitatory-inhibitory
(E-I) balance, studying this transfer function will provide valuable insight into the mechanisms
underlying neurodevelopmental and psychiatric disorders that stem from dysregulation of E-I
balance. We have developed an acute hippocampal slice preparation from the mouse that
allows us to independently evoke APs or EPSPs, from defined populations of inputs, within the
context of an intact circuit. We propose investigating the activity requirements for NPAS4
expression and the divergent genomic and synaptic regulation that follows from each type of
stimulus. We have used this approach to demonstrate that APs and EPSPs lead to NPAS4
expression with distinct spatio-temporal profiles and have extensive preliminary results
characterizing the unexpected underlying mechanisms. Using the methods developed for this
proposal, in combination with electrophysiology, optical, and sequencing techniques, we are
poised to determine how APs and EPSPs differentially impact activity-dependent gene
regulation and synapse function. This proposal is a significant departure from how IEG-TFs are
typically studied. The execution of these aims will yield important new insights into the
mechanics of activity-dependent gene regulation in neurons and how this biology is disrupted in
disorders of the brain such as Autism Spectrum Disorders and schizophrenia.

## Key facts

- **NIH application ID:** 10354848
- **Project number:** 3R01NS111162-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Brenda L Bloodgood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $76,452
- **Award type:** 3
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354848

## Citation

> US National Institutes of Health, RePORTER application 10354848, Molecular and cellular mechanisms underlying activity dependent gene regulation in neurons (3R01NS111162-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10354848. Licensed CC0.

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