# Mild traumatic brain injury alters interneuron structure and function

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $514,440

## Abstract

Project Summary
 This proposal seeks to better understand the contribution of cortical inhibitory interneuron subtypes to network
dysfunction after mild traumatic brain injury (mTBI) utilizing a well controlled and characterized mouse model,
the central fluid percussion injury. Our group has identified significant and differential dysfunction in neocortical
interneuron subtypes after mTBI in this model. Parvalbumin interneurons (PV) modulate gamma oscillations
recorded from EEG that is critical for sensory perception. The PV are particularly vulnerable after injury, with
10% being axotomized and the output from PV to local pyramidal neurons being significantly reduced. In contrast
somatostatin-containing interneurons (SOM) show little axotomy and have an increased output onto local
pyramidal neurons. In other disease models the link between the ratio of PV:SOM and altered gamma levels has
been well established. We hypothesize that injury also alters this ratio and that alteration underlies the increase
in resting gamma and the decrease in evoked gamma that we and others have observed. We will test that here
using chemogenetics and mutant mice with altered PV:SOM ratios. In addition we will test the link of that altered
gamma to an increased sensitivity to touch and lowered pain threshold. We further hypothesize that the reason
PV are vulnerable is due to the activation of microglia which subsequently degrade the perineuronal nets (PNN)
that normally surround the PV. Once the PNN are removed PV function is likely reduced due to reactive oxygen
species. Each aspect of these hypotheses will be tested by depleting microglia and by treating the oxidative
stress with N-Acetylcysteine. Outcome measures will include the power of the gamma recorded from EEG, pain
threshold via von Frey filaments, whisker nuisance test score, the percent of axotomized PV and SOM
interneurons, the intracellularly recorded function of the PV and SOM and the level of output from PV and SOM.
These studies will determine if this cellular dysfunction underlies the abnormal network function and altered
cognition after mTBI.

## Key facts

- **NIH application ID:** 10882090
- **Project number:** 2R01NS077675-11A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** JOHN GREER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $514,440
- **Award type:** 2
- **Project period:** 2011-09-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882090

## Citation

> US National Institutes of Health, RePORTER application 10882090, Mild traumatic brain injury alters interneuron structure and function (2R01NS077675-11A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10882090. Licensed CC0.

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