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  • Review Article
  • Published:

Circuits controlling vertebrate locomotion: moving in a new direction

Key Points

  • The central pattern generator (CPG) networks that generate relatively simple motor outputs are ideal experimental models for circuit analysis.

  • Locomotor CPGs in the ventral spinal cord function autonomously to generate repetitive patterns of oscillatory motor activity.

  • Recent progress has been made in identifying the neuronal components that make up the locomotor circuitry, with functional studies indicating that the locomotor CPG has a modular structure.

  • The development and assembly of the locomotor CPG is regulated by a genetic programme that operates in the embryonic spinal cord.

  • The merging of genetic analyses with systems approaches, coupled with new tools for imaging and regulating neuronal excitability, provides the means for a comprehensive analysis of these circuits.

  • The emerging phylogenetic relationship between neurons in the vertebrate spinal cord is providing key insights into the structure and function of the spinal motor circuitry.

Abstract

Neurobiologists have long sought to understand how circuits in the nervous system are organized to generate the precise neural outputs that underlie particular behaviours. The motor circuits in the spinal cord that control locomotion, commonly referred to as central pattern generator networks, provide an experimentally tractable model system for investigating how moderately complex ensembles of neurons generate select motor behaviours. The advent of novel molecular and genetic techniques coupled with recent advances in our knowledge of spinal cord development means that a comprehensive understanding of how the motor circuitry is organized and operates may be within our grasp.

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Figure 1: Organization of the locomotor system in vertebrates.
Figure 2: Rhythmic motor patterns underlying vertebrate locomotion.
Figure 3: Early development of the spinal cord.
Figure 4: Identified spinal interneurons in the embryonic mouse and zebrafish spinal cord.
Figure 5: Cre-dependent manipulation of V1 neurons in the mouse.

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Acknowledgements

Studies from the author's laboratory were supported by grants from the US National Institutes of Health (NS31978, NS37075 and NS31249), the Human Frontier Science Program and the Christopher Reeve Paralysis Foundation. Many thanks to D. McLean and J. Fetcho for the zebrafish schematic in figure 4. I apologize to those whose work I was unable to fully cite because of space constraints.

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Glossary

Central pattern generator

(CPG). A network of neurons that autonomously generates rhythmic patterns of activity.

Commissural neurons

Neurons whose axons cross from one side of the spinal cord to the other.

Ventricular zone

Innermost layer of the embryonic spinal cord that contains dividing progenitor cells.

Alar plate

Dorsal region of the ventricular zone in the embryonic spinal cord.

Lineage tracing studies

Techniques that allow the progeny of a cell in the embryo to be traced.

Fictive locomotion

Locomotion that is initiated in the absence of sensory feedback and descending control from the cortex.

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Goulding, M. Circuits controlling vertebrate locomotion: moving in a new direction. Nat Rev Neurosci 10, 507–518 (2009). https://doi.org/10.1038/nrn2608

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