# Role of TLR4 in Neuronal Excitability and Memory Function

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2021 · $46,036

## Abstract

Project Summary/Abstract
Toll-Like Receptor 4 (TLR4) is an innate immune receptor that is enhanced after brain injury and is implicated in
modulating excitability in the hippocampal dentate gyrus. We find that suppressing TLR4 after brain injury
reduces seizure susceptibility and memory deficits however has opposite effects in controls. In pilot studies,
TLR4 signaling increases synaptic inhibition to dentate granule cells in controls while reducing it after TBI,
indicating that inhibition may be central to the differential TLR4 effects in control and injured brain. TLR4 is
localized in dentate hilar neurons and co-localizes with somatostatin, not parvalbumin interneurons. Since TLR4
effects on inhibition correlate with dentate excitability and memory outcomes, I propose that cell type specific
and injury-state dependent TLR4 modulation of GABAergic synapses regulate dentate excitability and memory
processing. Using single/dual patch clamp recordings, cell-specific patterned optogenetic neuronal activation
and pharmacology in a rodent model of brain injury, I will resolve TLR4 regulation of synaptic inputs from SOM+
and PV+ neurons to granule cells in control and injured animals. Mice with cell-specific deletion of TLR4 will be
subject to brain injury and probed for TLR4 regulation of network function using a novel in-vitro temporal pattern
separation assay and behavioral pattern separation tasks. The study will advance basic knowledge on immune
regulation of excitability and memory processing and identify potential targets to limit post-traumatic changes in
neuronal activity.

## Key facts

- **NIH application ID:** 10316103
- **Project number:** 1F31NS120620-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Susan T Nguyen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316103

## Citation

> US National Institutes of Health, RePORTER application 10316103, Role of TLR4 in Neuronal Excitability and Memory Function (1F31NS120620-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316103. Licensed CC0.

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