# Lesion and activity dependent corticospinal tract plasticity

> **NIH NIH R01** · CITY COLLEGE OF NEW YORK · 2022 · $42,953

## Abstract

Corticospinal tract (CST) injury deprives spinal circuits of movement control signals. This leads to loss of
function—muscle weakness and paralysis—and gain of dysfunction—including hyperreflexia and spasticity. To
repair the CST after injury and restore motor control, it is necessary to abrogate the impairments due to both the
loss of function and gain of dysfunction following injury. Our research during the prior funding period shows that
activity-dependent processes underlie both the loss of function and gain of dysfunction after CST injury. This
finding provides the foundation for developing new therapeutic neuromodulatory approaches to target activity
dependence using motor cortex (MCX) stimulation and transspinal direct current stimulation (tsDCS).
 MCX stimulation after injury is effective in CST repair and motor recovery. In Aim 1 we will determine the
most effective MCX neuromodulation treatment to produce persistent structural and functional plasticity of the
corticospinal system. Using different stimulation patterns, we will ask if efficacy depends on recruiting CST
axon growth-promoting signaling. Using optogenetics to identify activated CST axons, we will test how
stimulation patterns determine anatomical and physiological outcomes. Knowing that recovery is more than
CST sprouting, we will ask if efficacy depends on producing long-term physiological changes in spinal circuits.
 We recently showed that selective CST injury or MCX inactivation produces trans-neuronal loss of spinal
cholinergic interneurons and that this loss can be rescued by spinal activation. In Aim 2 we will determine how
MCX neuromodulation regulates transneuronal segmental circuit remodeling after injury to promote spinal
circuit repair. We will ask how CST injury impacts the major class of excitatory premotor interneurons of the
CST. We will test if MCX stimulation ameliorates trans-neuronal circuit changes and then examine the interplay
of repair strategies differentially targeting microglial-based spinal circuit remodeling and CST sprouting
 In Aim 3 we will harness the differential actions of tsDCS on spinal circuits to enhance repair and
rehabilitation efficacy after cervical SCI. Spinal circuits integrate motor control signals with afferent information.
After SCI, with the loss of motor pathways, spared afferent feedback dominates segmental circuit function. We
recently showed that afferent competition diminishes CST connection strength, to reinforce afferent over
integrated control. We will use the differential actions of tsDCS to promote spared CST function and weaken
potentially “runaway” afferent input, to rebalance segmental control. We will develop a novel strategy that
combines neuromodulation-based repair with neuromodulation-assisted rehabilitation to promote recovery.
 Successful completion of our studies will advance our understanding of the mechanisms of impairment and
the mechanisms underlying novel neuromodulatory repair strategies after SCI. R...

## Key facts

- **NIH application ID:** 10640586
- **Project number:** 3R01NS064004-14S1
- **Recipient organization:** CITY COLLEGE OF NEW YORK
- **Principal Investigator:** John H Martin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,953
- **Award type:** 3
- **Project period:** 2009-05-19 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10640586

## Citation

> US National Institutes of Health, RePORTER application 10640586, Lesion and activity dependent corticospinal tract plasticity (3R01NS064004-14S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10640586. Licensed CC0.

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