# Optical dissection of intracortical circuits supporting motor recovery after spinal cord injury

> **NIH NIH R01** · WINIFRED MASTERSON BURKE MED RES INST · 2020 · $445,979

## Abstract

PROJECT SUMMARY: Cortical motor networks are a critical, if often overlooked, mediator of motor recovery after
spinal cord injury (SCI). Cortical networks are required for instructing output through the corticofugal
projections to the brainstem and spinal cord, and the plasticity of these networks will be indispensable for re-
learning how to use the spinal circuits altered by SCI or therapeutic intervention. Rehabilitation is necessary for
both the recovery of corticospinal-dependent forelimb function and the commensurate reorganization of
disrupted cortical motor maps. It remains unknown what the underlying circuit mechanisms are that support
cortical reorganization after SCI, or whether such broad reorganization is necessary to support functional
recovery. The long-term goal is to develop therapeutic interventions that take advantage of cortical plasticity to
promote recovery from SCI. The overall objective for this proposal is to identify the intracortical circuitry
responsible for restoring skilled forelimb function. The central hypothesis is that latent intracortical connections
projecting from de-efferented hindlimb to forelimb areas are required for rehabilitation-mediated recovery of
skilled forelimb function after cervical SCI. The rationale for the proposed research is that the knowledge of
how the motor cortex incorporates circuit changes after SCI will help us to target new therapies for motor
recovery. The following three specific aims are proposed: 1) Record the endogenous activity from intracortical
neurons during rehabilitation-mediated recovery from SCI; 2) Determine the structural changes in horizontal
connections during rehabilitation from SCI; and 3) Identify the contribution of horizontal connections to motor
recovery after SCI. For the first aim, the approach will be to record activity from interconnected hindlimb and
forelimb motor regions during skilled forelimb behavior in order to determine their response to rehabilitation
from SCI. In the second aim, the approach will be to image structural changes of intracortical axons and
dendritic spines in vivo longitudinally during rehabilitation from SCI. In the third aim, the approach will be to 1)
silence interconnected neurons in awake, behaving mice to determine their contribution to recovery, and 2)
stimulate interconnected neurons and measure forelimb motor evoked potentials. The proposed studies are
innovative in that they shift the focus of spinal cord injury research from axon regeneration to the intracortical
networks required for interpreting the changes in spinal cord circuitry. The proposed studies are significant
because they will provide a detailed understanding of the mechanisms of circuit remodeling that influence
recovery. The expectation is that completion of the proposed research will determine the extent to which
intracortical neuron plasticity underlies cortical motor map reorganization and supports functional recovery after
SCI. These findings will establi...

## Key facts

- **NIH application ID:** 9956722
- **Project number:** 5R01NS105725-02
- **Recipient organization:** WINIFRED MASTERSON BURKE MED RES INST
- **Principal Investigator:** Edmund R Hollis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,979
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956722

## Citation

> US National Institutes of Health, RePORTER application 9956722, Optical dissection of intracortical circuits supporting motor recovery after spinal cord injury (5R01NS105725-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9956722. Licensed CC0.

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