# Specific spinal locomotor circuit alterations induced by epidural stimulation

> **NIH NIH R21** · DREXEL UNIVERSITY · 2020 · $415,875

## Abstract

ABSTRACT
Epidural stimulation (ES) has shown great promise for the restoration of motor functioning after SCI both clinically
and in animal models. Despite its success in activating silenced circuits below the level of the injury allowing for
movement of paralyzed limbs, the mechanisms contributing to its long-term effects are unknown. Central pattern
generators (CPG) in the lumbar spinal cord control both the rhythm and pattern of locomotion. CPGs are below
the level of most injuries, and, therefore, relatively intact and accessible by ES. Recent efforts in our lab to
determine the mechanisms by which ES exerts its beneficial effects at the level of the spinal locomotor circuit
have revealed alterations in sensory pathways to the locomotor CPG following SCI which are either prevented
or reversed by ES at intensities that are subthreshold for motor activation (sub-motor-threshold ES) while the
mouse is on a treadmill. In a complete transection SCI model, these circuit alterations are evident despite the
apparent lack of locomotor-related hindlimb activity on the treadmill. Our current proposal will directly test
whether sub-motor-threshold ES alone is sufficient to induce beneficial plasticity and/or prevent maladaptive
plasticity at the level of spinal locomotor circuits in mice. In humans, ES alone does not support walking without
extensive concomitant rehabilitative training since the afferent activation by ES occludes the normal
proprioceptive sensory signal. Additionally, although there may be a post-injury critical window for maximum
plasticity, extensive activity-based rehabilitation is often not possible at these early time points. If the circuit
plasticity observed with ES occurs in the absence of motor training, this will suggest sub-motor-threshold ES as
a method that could be used for bedridden patients as a bridge for future rehabilitation. For the second aim of
the proposal, we will determine the neural substrates of the alterations in spinal sensory pathways to locomotor
circuits that are evident after SCI and after ES. We will focus on CPG neurons and inhibitory neurons interposed
between CPG neurons and primary afferents. Together, we propose to reveal whether sub-motor-threshold ES
is a potential strategy to alter spinal circuits prior to the time when activity-based therapies are feasible. If this is
the case, it will suggest a treatment strategy that can be used either in place of or as a bridge until active
rehabilitation is possible. Further, we propose to identify a key population of neurons involved in this plasticity,
thereby suggesting a specific target of future cell-specific therapeutics.

## Key facts

- **NIH application ID:** 10041067
- **Project number:** 1R21NS118226-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kimberly J Dougherty
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,875
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041067

## Citation

> US National Institutes of Health, RePORTER application 10041067, Specific spinal locomotor circuit alterations induced by epidural stimulation (1R21NS118226-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10041067. Licensed CC0.

---

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