# Tracking the evolution of synaptic dysplasticity after early life seizures

> **NIH NIH R37** · UNIVERSITY OF PENNSYLVANIA · 2020 · $1,612,421

## Abstract

PROJECT SUMMARY
 Multiple lines of clinical and experimental evidence suggest that seizures in early life can be associated
with long lasting cognitive and behavioral deficits. In rodent models, we have showed that early life seizures
(ELS) impair normal synaptic plasticity, critical period plasticity, later life learning and social behavioral deficits.
Improved understanding as to how seizure activity and hyperexcitable networks dysregulate synaptic plasticity
will be required to develop new therapeutic strategies in this clinical space where no current cure exists.
 We will focus on dysplasticity related to alterations of the excitatory synaptic glutamate receptor and its
related signaling pathways. Tracking alterations of synaptic glutamate receptors in neurons activated by ELS is
a specific challenge given that they occur in the midst of the synaptic critical period, the refinement of synaptic
connections and the dispersion of neurons with development, which makes it difficult to localize neurons for
functional studies later in life, despite the persistence of impaired synaptic plasticity and cognitive deficits.
Similarly, sampling of a neuronal population for gene and protein expression may fail to show alterations
occurring in a small, critical, subset of cells. To address these issues, we have adapted a method to permanently
label cells activated by ELS in mice so that we can measure synaptic responses, gene and protein expression
at a single neuron level, and then differentially label them during subsequent later life seizure (LLS) events.
Using our ELS models, we aim to determine whether neurons activated by ELS have persistent, life-long,
alterations of glutamate receptor function associated with impaired synaptic plasticity and hyperexcitability
compared to neurons from no-seizure control mice (Aim 1). We will correlate these functional changes with
measurements of gene and protein expression related to glutamate receptor function compared to neurons from
no-seizure control mice (Aim 2). Finally, we will determine whether neurons activated by ELS are differentially
affected by a second later life seizure (LLS) in adulthood compared to control neurons in seizure free mice (Aim
3). The synapse is a convergence point for the likely many upstream derangements of network function,
and therefore an ideal target of study. We hypothesize that tracking the evolution of changes over time in
select neuronal populations following ELS will allow us to both “stage” the evolution of changes and identify new
therapeutic targets for this comorbidity and consequence of seizures in the immature brain.

## Key facts

- **NIH application ID:** 9996219
- **Project number:** 1R37NS115439-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Frances E Jensen
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,612,421
- **Award type:** 1
- **Project period:** 2020-04-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996219

## Citation

> US National Institutes of Health, RePORTER application 9996219, Tracking the evolution of synaptic dysplasticity after early life seizures (1R37NS115439-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9996219. Licensed CC0.

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