# CORTICOSPINAL MECHANISMS FOR HIGH FAT DIET IMPEDING STROKE RECOVERY

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $56,566

## Abstract

ABSTRACT
The goal of this project is to provide funding support to an excellent young scientist who qualifies as a
underrepresented individual per NIH criteria. This funding will provide key support to allow this individual to
contribute to stroke research and form an independent career following their professional goals to become a
principal investigator of their own laboratory. Stroke is a key health issue and its chronic motor impairments
continue to be a major source of disability and detriment to activities of daily living and quality of life. An important
knowledge gap for this health issue is the need to understand the neuronal control of volitional lower extremity
movement both during healthy and stroke-injured conditions. This proposal addresses this knowledge gap by
using two sophisticated brain stimulation techniques to activate and test the lower extremity cortical motor control
pathway. In Aim 1, we propose to use electrical Long Train Intracortical Microstimulation (LT-ICMS) to stimulate
motor cortex as it has not previously been used to study stroke recovery in laboratory mice. Further, LT-ICMS
produces more complex motor outputs (relative to other forms of brain stimulation), that may be more
ethologically-relevant, and the timing of its neural activation may more closely match natural brain activity during
wake-behaving movement. We seek to expand on preliminary findings that suggest there are specific forms of
LT-ICMS-measured cortical remodeling during poor and exceptional stroke recovery that may guide how we
treat individuals after stroke. In Aim 2, we propose to use optogenetics to specifically stimulate the corticospinal
circuitry responsible for movement of the lower extremities. The canonical view of the corticospinal tract is that
it is a synaptic circuit, from layer 5 pyramidal cells (L5PCs) in motor cortex, to spinal motor neurons that
themselves signal skeletal muscle. L5PCs that project to lumbar spinal cord (lumbar-projecting) are thought to
control lower extremity function. Here we propose to introduce photo-sensitive channelrhodopsin variant 2
(ChR2) into lumbar-projecting L5PCs by back-tracing these neurons from lumbar spinal cord using adeno-
associated virus of retrograde serotype (AAVrg). This AAVrg targets axonal terminals and results in genetic
manipulation of the targeted cells without spreading further across additional synapses. We then plan to deliver
intracortical optical blue light, using the same pulse parameters as electrical LT-ICMS, to selectively activate
lumbar-projecting L5PCs in motor cortex by stimulating their artificial ChR2. Given that blue light stimuli will
selectively activate neurons that express ChR2, this approach will allow direct testing of corticospinal circuitry
responsible for movement of the lower extremities using highly-specific targeting of this cell population in order
to guide future therapeutic treatment based on its precise deficits after stroke. Together, these aims prov...

## Key facts

- **NIH application ID:** 10302996
- **Project number:** 3R01NS114651-02S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** JEFFERY ALLEN BOYCHUK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $56,566
- **Award type:** 3
- **Project period:** 2021-04-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302996

## Citation

> US National Institutes of Health, RePORTER application 10302996, CORTICOSPINAL MECHANISMS FOR HIGH FAT DIET IMPEDING STROKE RECOVERY (3R01NS114651-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10302996. Licensed CC0.

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