# Electrochemical assessment of behaviorally relevant circuit function after TBI

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $335,781

## Abstract

Project Summary/Abstract
Traumatic brain injuries (TBI) frequently result in persisting post-traumatic neurological consequences,
including hypersensitivity to light, with limited effective treatments. Vision is a primary sensory modality in
humans, similar to whisker sensation in rodents. Primary sensory modalities incorporate a large portion of the
brain for processing, making them susceptible to diffuse TBI. The goal of this proposal is to employ an
experimental rodent model of diffuse TBI that highlights sensory deficits to evaluate delayed alterations in
glutamate signaling as a universal consequence of TBI and its potential for modulation. Using this model in
preliminary results the PI has demonstrated that TBI induces late-onset sensory hypersensitivity to whisker
stimulation by post-injury day (PID) 28 that persists to PID 56. This injury-induced sensory hypersensitivity is
measured using the established Whisker Nuisance Task (WNT), where whisker stimulation results in active
evasion and aberrant responses in injured rats compared to ambivalence or curiosity in uninjured rats. Since
the whisker circuit is glutamatergic, this research team implemented electrochemical microelectrode array
technology, capable of real-time measurements of glutamate neurotransmission in vivo, for recordings within
the relays of the whisker circuit in anesthetized rats. The PI reported that WNT scores positively correlate to
the magnitude of potassium (KCl)-evoked glutamate release in the somatosensory thalamus and cortex.
Evoked-glutamate release was sensitive to Ω-conotoxin, indicating hypersensitive presynaptic glutamate
release as a potential mechanism for whisker hypersensitivity. Also, 3D reconstruction of neuron morphology
shows increased numbers of terminating dendrites within the thalamus at PID 28, providing a potential source
for increased glutamate release. KCl-evoked glutamate responses are required in anesthetized studies since
whisker stimulation-evoked glutamate responses are suppressed by anesthesia. Thus, real-time recordings of
glutamate neurotransmission in the awake, freely-moving rat permits the evaluation of whisker stimulation-
evoked glutamate responses during the WNT. This has led to the central hypotheses that TBI-induced
sensory hypersensitivity arises from altered glutamate signaling in sensory circuits and that early rehabilitation
will restore circuit function and alleviate behavioral symptoms. To test these hypotheses adult male and female
rats will be subjected to diffuse TBI by midline fluid percussion and evaluated for: 1) the influence of sex on
late-onset sensory hypersensitivity to whisker stimulation and glutamate neurotransmission; 2) whisker
stimulated-evoked glutamate release in awake, freely-moving rats, with respect to time post-diffuse TBI, and 3)
evidence that circuit-directed rehabilitation, focused on the whiskers, can mitigate hypersensitive glutamate
release and concurrent behavioral sensory hypersensitivity. Im...

## Key facts

- **NIH application ID:** 10070652
- **Project number:** 5R01NS100793-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Theresa Currier Thomas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,781
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070652

## Citation

> US National Institutes of Health, RePORTER application 10070652, Electrochemical assessment of behaviorally relevant circuit function after TBI (5R01NS100793-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10070652. Licensed CC0.

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