Acetylcholine and spinal locomotor networks: The insider.

Théo Mille,Sandrine S Bertrand,Camille Quilgars,Jean-René Cazalets

doi:10.14814/phy2.14736

Abstract

This article aims to review studies that have investigated the role of neurons that use the transmitter acetylcholine (ACh) in controlling the operation of locomotor neural networks within the spinal cord. This cholinergic system has the particularity of being completely intraspinal. We describe the different effects exerted by spinal cholinergic neurons on locomotor circuitry by the pharmacological activation or blockade of this propriospinal system, as well as describing its different cellular and subcellular targets. Through the activation of one ionotropic receptor, the nicotinic receptor, and five metabotropic receptors, the M1 to M5 muscarinic receptors, the cholinergic system exerts a powerful control both on synaptic transmission and locomotor network neuron excitability. Although tremendous advances have been made in our understanding of the spinal cholinergic system's involvement in the physiology and pathophysiology of locomotor networks, gaps still remain, including the precise role of the different subtypes of cholinergic neurons as well as their pre‐ and postsynaptic partners. Improving our knowledge of the propriospinal cholinergic system is of major relevance to finding new cellular targets and therapeutics in countering the debilitating effects of neurodegenerative diseases and restoring motor functions after spinal cord injury.

Highlights

IntroductionTo generate locomotor activity, neurons are organized into highly specialized networks called central pattern generators (CPGs), which are endowed with the ability to generate in an autonomous manner both the rhythm itself and the pattern (the precise sequence of muscular activation) of locomotor activity
To generate locomotor activity, neurons are organized into highly specialized networks called central pattern generators (CPGs), which are endowed with the ability to generate in an autonomous manner both the rhythm itself and the pattern of locomotor activity
We have recently shown that the exogenous application of oxotremorine on isolated thoracic segments induces the expression of a slow motor rhythm in thoracic ventral roots (Sourioux et al, 2018)

Summary

Introduction

To generate locomotor activity, neurons are organized into highly specialized networks called central pattern generators (CPGs), which are endowed with the ability to generate in an autonomous manner both the rhythm itself and the pattern (the precise sequence of muscular activation) of locomotor activity. To enable the continual adaptation of the motor command to external and internal demands, both CPG neurons and MNs are targeted by sensory, intraspinal, and supraspinal synaptic inputs that are extremely diverse in terms of neurochemical phenotype. A distinction has been made between neurotransmitters that sustain fast chemical transmission between neurons through the activation of ion channel receptors: glutamate, GABA and glycine, and neuromodulators: monoamines, acetylcholine, peptides... It is well acknowledged that this distinction is not so clear, with many neuroactive compounds being capable of activating both ionotropic and metabotropic receptors simultaneously.

Objectives

Conclusion