# The role of propriospinal neurons in the recovery of posture after spinal cord injury

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $569,959

## Abstract

Project Summary
Neurons that control rhythmic movements like walking reside within the spinal cord in the central pattern
generator (CPG), and thus understanding this CPG has been a major focus of rehabilitation efforts after spinal
cord injury (SCI). However, the prerequisites for walking are steady postural tone and ability to stand, which
are permanently lost following spinal cord injury. While standing to reach or make wheelchair transfers is
arguably a more important function to restore than walking after SCI, little is known about the spinal circuits
that control posture. However, in the course of our recent survey of neurons that generate muscle spasms in
mice, we unexpectedly found that excitatory propriospinal commissural neurons (PSC neurons) that express
the Sim1 transcription factor (V3 neurons) produce robust standing when they are optogenetically, including in
mice that are otherwise paralysed after SCI. PSC neurons may be ideally suited to maintaining posture, as
they directly innervate extensor motoneurons throughout the limb and axial muscles, and are innervated
extensively by sensory and supraspinal inputs, seemingly bypassing the CPG, though we know little about
their control. Since PSC neurons (including V3) have unique anatomical and functional connections and
properties, they can be readily identified in mice and cats, and so we will start by recording the firing properties
of these neurons prior to injury in the decerebrate unanesthetized animals that spontaneously exhibit a
standing posture. We will test the hypothesis that prior to SCI, PSC neurons are driven tonically by supraspinal
inputs to maintain posture and phasically by sensory feedback to correct for disturbances, but this supraspinal
drive is lost with acute SCI. We also hypothesize that after chronic SCI increased excitability in these neurons
helps restore some phasic sensory-evoked postural tone that may be promoted by stimulating nerves that
innervate PSC neurons or by direct optogenetic V3 activation. This will be examined both in awake mice with
optogenetic activation or inhibition of V3 neurons where we will record limb kinematics and EMG, and in the
isolated whole adult in vitro spinal cord where we will making direct intracellular recordings from V3 neurons
and the motoneurons they innervate. Finally, we will examine whether the postural standing that can be
obtained by sensory evoked V3 neuron activation can be used as a basis for training mice to walk after SCI,
and explore whether the action of treatments like epidural spinal cord stimulation function by activating PSC
neurons. Overall, these experiments will shed light on how spinal postural motor circuits are controlled by
propriospinal neurons, and how these neurons can be harnessed to develop new treatments for SCI.

## Key facts

- **NIH application ID:** 10891019
- **Project number:** 1R01NS132487-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** David James Bennett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $569,959
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891019

## Citation

> US National Institutes of Health, RePORTER application 10891019, The role of propriospinal neurons in the recovery of posture after spinal cord injury (1R01NS132487-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10891019. Licensed CC0.

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