# The Role of Corticospinal Neurons in the Recovery of Dexterous Forelimb Function After Spinal Cord Injury

> **NIH NIH R01** · WINIFRED MASTERSON BURKE MED RES INST · 2024 · $534,701

## Abstract

PROJECT SUMMARY: The adverse effects of spinal cord injury (SCI) on corticospinal function are not restricted
to the damaged spinal cord, but also disrupt motor representations within the cortex. SCI results in altered
cortical maps that represent motor output, with representations above the level of injury expanding into
affected cortical areas. Rehabilitation is necessary for both the recovery of corticospinal-dependent forelimb
function and the commensurate reorganization of disrupted cortical motor maps. Both the underlying circuit
mechanisms that support cortical reorganization after SCI as well as the necessity for the reorganized circuitry
to support functional recovery, remain unknown. For injured corticospinal neurons to contribute to functional
recovery, they must be integrated into cortical motor networks. The long-term goal is to develop therapeutic
interventions for supporting functional recovery after SCL The overall obiective for this proposal is to determine
how specific rehabilitation after SCI promotes remodeling of corticospinal circuits and the contribution of injured
corticospinal neurons to motor recovery. The central hypothesis is that corticospinal-dependent rehabilitation
after SCI directs the structural remodeling of injured corticospinal neurons resulting in their incorporation into
functional motor ensembles. The rationale for the proposed research is that determining the properties of
rehabilitative training that promote successful corticospinal circuit incorporation into cortical motor networks
after SCI will be crucial for developing effective rehabilitative strategies. The following three specific aims are
proposed: 1) Identify the nature of structural and connectivity changes that occur in injured corticospinal
neurons during rehabilitation-mediated recovery from SCI; 2) Identify the changes in the functional connectivity
of injured corticospinal neurons during rehabilitation-mediated recovery from SCI; and 3) Identify the
contribution of injured corticospinal neurons to motor recovery after SCL For the first aim, the approach will be
to image structural changes of injured corticospinal dendritic arbors in response to rehabilitation. In the second
aim, the approaches will be to use 2-photon imaging to record the activity of injured corticospinal neurons
during rehabilitation and to use retrograde transsynaptic tracing to identify presynaptic inputs. In the third aim,
the approach will be to optogenetically control injured corticospinal neurons in awake, behaving mice to
determine their contribution to recovery. The proposed studies are innovative in that they shift the focus of
spinal cord rehabilitation onto the circuit mechanisms of cortical network plasticity. The proposed studies are
significant because they will elucidate the mechanisms by which circuit remodeling influences recovery and will
inform combinatorial strategies that target cortical plasticity to fully realize the effects of axonal sprouting and
r...

## Key facts

- **NIH application ID:** 10990748
- **Project number:** 1R01NS136711-01A1
- **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:** 2024
- **Award amount:** $534,701
- **Award type:** 1
- **Project period:** 2024-05-05 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990748

## Citation

> US National Institutes of Health, RePORTER application 10990748, The Role of Corticospinal Neurons in the Recovery of Dexterous Forelimb Function After Spinal Cord Injury (1R01NS136711-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10990748. Licensed CC0.

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