# Afferent modulation of rhythm-generating neurons in the spinal locomotor central pattern generator

> **NIH NIH F30** · DREXEL UNIVERSITY · 2020 · $50,520

## Abstract

ABSTRACT
Rhythmic motor activities including walking, running and swimming are controlled by spinal circuits known as
central pattern generators (CPGs). These circuits integrate descending command signals from the brain and
ascending feedback signals indicating muscle length and force. The basic motor pattern for walking is generated
by a CPG located within the lumbar spinal cord. Although the descending commands are compromised in spinal
cord injury, afferent sensory signals retain CPG access and are thought to be recruited in gait rehabilitation
therapies including treadmill training and epidural stimulation. More effective engagement of CPG elements via
afferent signaling may improve therapeutic outcomes. Extensive data from the cat and the rat have identified hip
extension and ankle load as strong modulators of stance and swing phase timing. Activation of these afferents
perturb the gait cycle in ways that may or may not persist as a phase angle shift in subsequent cycles. These
results have suggested a two-layer CPG structure in which a rhythm-generating (RG) layer acts as the
metronome and directs a pattern-forming (PF) layer that recruits motoneurons. Sensory inputs to the RG neurons
are expected to have the most profound effects on locomotor function. However, the organization of sensory
feedback within the CPG is poorly understood, in part because the cellular identity and connectivity of CPG
circuit elements have only begun to be described within the last decade. Recently, a population of neurons that
are Shox2+/Chx10- (Shox2RG) has been putatively identified as part of the RG layer. The goal of the proposed
project is to use a combination of biological and computational approaches to explore how sensory afferent
inputs are organized within the RG layer of the CPG and contribute to stance/swing phase duration and onset.
We hypothesize that evoked polysynaptic inputs to Shox2RG neurons underlie the afferent modulation of gait
timing. We have preliminary data showing that stimulation of specific proprioceptive afferents results in
postsynaptic responses in many Shox2 neurons. We will test integration of information from specific afferents in
Shox2RG neurons by separately stimulating nerves innervating flexor and extensor muscles at the hip and ankle
during visually-guided patch clamp of Shox2RG neurons in isolated spinal cord preparations. Intermediate
neurons in these polysynaptic pathways will be tested to see whether convergence of afferent input is mediated
at the level of Shox2RG neurons or before. The pattern of input measured in the quiescent preparation will be
tested and compared to that obtained during fictive locomotion. These data will be integrated into a computational
model of the CPG to test for the sufficiency of the experimental data to account for observed sensory modulation
of CPG timing and activation. Results are expected to provide new insights into the fundamental operation of
feedback systems affecting RG circuits ...

## Key facts

- **NIH application ID:** 10005503
- **Project number:** 5F30NS110199-03
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Erik Zhi-Chong Li
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-09-21 → 2022-06-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005503

## Citation

> US National Institutes of Health, RePORTER application 10005503, Afferent modulation of rhythm-generating neurons in the spinal locomotor central pattern generator (5F30NS110199-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10005503. Licensed CC0.

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