# Mechanisms of locomotor rhythm generation in rodent spinal cord

> **NIH NIH R01** · DREXEL UNIVERSITY · 2022 · $523,074

## Abstract

ABSTRACT
Locomotion is a fundamental behavior that allows humans and animals to move through their environments and
is critically involved in all aspects of life. This behavior is impeded in a number of diseases, disorders, and
injuries, including spinal cord injury, stroke, and various ataxias. All of the essential circuity to generate locomotor
rhythm and pattern is located in the thoracolumbar spinal cord, most often below the level of neural damage.
These circuits can be accessed directly via various central and peripheral stimulation methods, including but not
limited to epidural stimulation. Rhythm generating circuits are the entry point for initiation and control of
locomotion, affect all downstream neurons related to locomotion, and, therefore, are the first step in establishing
spinal control of locomotion. Successful activation of the rhythm generator clinically has been hampered because
the mechanisms by which spinal neuronal circuits generate coordinated rhythmic output remain poorly
understood and represents a major gap in our understanding of neural control of movement. The generation of
rhythmic motor behaviors is based on a triad involving: (1) specific “rhythmogenic” properties allowing individual
neurons to generate rhythmic oscillations, (2) mutual excitatory interactions to synchronize neuronal activity into
rhythmic populational bursting, and (3) network inhibition to coordinate activity between different neuronal
populations, which can both shape locomotor pattern and control frequency. Triad components are highly
interconnected and the involvement of each component is condition-dependent. The proposed study will use
highly integrated electrophysiological, pharmacological, genetic, and computational approaches to systematically
explore the specific contributions of these mechanisms and the interactions between them, in the generation and
patterning of the locomotor rhythm. Utilizing spinal neurons identified in transgenic mice by the transcription
factor Shox2 as a representative rhythm generating population, we will test the overarching hypothesis that rhythm
generating mechanisms in the spinal cord involve interplay between the triad of cellular, population, and network
properties, whose contribution to rhythmogenesis is interdependent, leading to flexibility and adaptability seen
as alterations in the relative balance of the triad in different conditions. We will first determine the voltage-gated
currents underlying spontaneous cellular oscillations in adult Shox2 neurons. We will then assess excitatory
interactions between rhythm generating neurons. Lastly, we will establish the role of ipsilateral and contralateral
network interactions in regulating locomotor frequency, and determine the operation of these pathways during
afferent-evoked locomotion. Together, our multidisciplinary study will reveal mechanisms of rhythm generation,
establish the first mammalian locomotor neural network model based on “real” rhythm genera...

## Key facts

- **NIH application ID:** 10605444
- **Project number:** 1R01NS130799-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kimberly J Dougherty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $523,074
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10605444

## Citation

> US National Institutes of Health, RePORTER application 10605444, Mechanisms of locomotor rhythm generation in rodent spinal cord (1R01NS130799-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10605444. Licensed CC0.

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