# Modulation of cortical networks, a new approach to spinal cord injury rehabilitation

> **NIH NIH DP2** · WINIFRED MASTERSON BURKE MED RES INST · 2020 · $11,354

## Abstract

Project Summary/Abstract
 The corticospinal pathway is a pivotal mediator of voluntary motor control in humans and restoring
corticospinal motor function after spinal cord injury remains one of the most substantial challenges facing
translational and clinical neuroscience today. Regardless of the approach taken to alleviate the interruption of
corticospinal axons, functional recovery will rely on the plasticity of the cortical motor network to incorporate the
remodeled or replaced circuit. The creation of novel therapeutic interventions for the recovery of function after
injury will have to be coupled to an understanding of the cellular and subcellular mechanisms that support cortical
motor network remodeling and incorporation of injured neurons. Only recently have the tools necessary to
answer these critical questions been developed. The long-term goal is to develop novel therapeutic interventions
for the recovery of function after spinal cord injury through an understanding of the cellular and subcellular
mechanisms that drive neural circuit remodeling. The overall objective for this proposal is to identify
neuromodulatory mechanisms of motor map plasticity that correlate with recovery of skilled motor function and
to determine the relationship between cortical network changes and corticospinal circuit remodeling after cervical
spinal cord injury. The central hypothesis is that cholinergic input directly to corticospinal motor neurons is
required for functional integration of corticospinal circuit changes into de novo motor networks after spinal cord
injury. The rationale for the proposed research is that once the role of cholinergic activity in rehabilitation after
spinal cord injury is defined, it is likely to provide new opportunities for pharmacological modulation and pairing
with treatments that enhance corticospinal axon regeneration. The first approach will be to use cytotoxic lesions
and optogenetic/chemogenetic control of relevant subcortical circuitry to modulate known mediators of motor
learning while using two-photon microscopy to assess the functional incorporation of injured corticospinal
neurons by measuring activity and structural changes during rehabilitation in awake, behaving animals. The
second approach will be to define the molecular mechanisms and the cellular location of signaling events that
underlie motor learning, and likely motor rehabilitation. The proposed studies are innovative in that they shift the
focus of spinal cord rehabilitation onto the circuit mechanisms of cortical network plasticity and will have far-
reaching importance in translating treatments for both acute and chronic injuries to motor networks. The
proposed studies are significant because they will elucidate the mechanisms by which circuit remodeling
influences recovery, which will have far-reaching importance in translating treatments for both acute and chronic
injuries to cortical motor networks. The expectation is that completion of the proposed...

## Key facts

- **NIH application ID:** 10243081
- **Project number:** 3DP2NS106663-01S2
- **Recipient organization:** WINIFRED MASTERSON BURKE MED RES INST
- **Principal Investigator:** Edmund R Hollis
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $11,354
- **Award type:** 3
- **Project period:** 2020-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10243081

## Citation

> US National Institutes of Health, RePORTER application 10243081, Modulation of cortical networks, a new approach to spinal cord injury rehabilitation (3DP2NS106663-01S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10243081. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*