State-Dependent Modulation of Locomotion by GABAergic Spinal Sensory Neurons

TL;DR

This study reveals how GABAergic CSF-contacting neurons in the spinal cord modulate locomotion in zebrafish by influencing central pattern generators, acting in a state-dependent manner to either initiate or inhibit movement.

Contribution

It uncovers the functional connectivity and modulatory role of CSF-cNs in spinal locomotor circuits, highlighting their influence on CPGs and locomotion control.

Findings

CSF-cNs form GABAergic synapses onto V0-v interneurons.

Activation of CSF-cNs induces delayed slow locomotion.

Selective activation disrupts rostrocaudal propagation of locomotor signals.

Abstract

The cerebrospinal fluid (CSF) constitutes an interface through which chemical cues can reach and modulate the activity of neurons located at the epithelial boundary within the entire nervous system. Here, we investigate the role and functional connectivity of a class of GABAergic sensory neurons contacting the CSF in the vertebrate spinal cord and referred to as CSF-cNs. The remote activation of CSF-cNs was shown to trigger delayed slow locomotion in the zebrafish larva, suggesting that these cells modulate components of locomotor central pattern generators (CPGs). Combining anatomy, electrophysiology, and optogenetics in vivo, we show that CSF-cNs form active GABAergic synapses onto V0-v glutamatergic interneurons, an essential component of locomotor CPGs. We confirmed that activating CSF-cNs at rest induced delayed slow locomotion in the fictive preparation. In contrast, the activation of CSF-cNs promptly inhibited ongoing slow locomotion. Moreover, selective activation of rostral CSF-cNs during ongoing activity disrupted rostrocaudal propagation of descending excitation along the spinal cord, indicating that CSF-cNs primarily act at the premotor level. Altogether, our results demonstrate how a spinal GABAergic sensory neuron can tune the excitability of locomotor CPGs in a state-dependent manner by projecting onto essential components of the excitatory premotor pool.