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Decoding the organization of spinal circuits that control locomotion

Key Points

  • Locomotion is a complex motor act that, to a large degree, is controlled by neuronal circuits in the spinal cord. Using a systems neuroscience approach in several model systems of non-limbed and limbed animals, important advances have been made in revealing the functional organization of the spinal locomotor networks.

  • The key circuit elements in the spinal locomotor networks are the rhythm-generating circuits and the pattern-generating circuits, which include circuits that control bilateral muscle activity, and circuits that control flexor–extensor muscles in limbed animals.

  • Comparison of the network organization of the key circuit elements in limbed and non-limbed animals reveals both commonalities and differences in organization.

  • The commonalities extend to the basic components of inhibitory left–right alternating circuits and excitatory neurons involved in rhythm generation.

  • The differences include left–right alternating circuitries that have multiple components in legged animals compared with the control of axial muscles in fish where one component dominates, rhythm-generating neurons that originate from developmentally diverse progenitors in fish and mice, and elaborated reciprocal network circuits involved in the flexor–extensor coordination that is found in legged animals, which do not have direct counterparts in non-legged animals.

  • Locomotor networks, whether they control swimming or over-ground locomotion, are built around modules of rhythm- and pattern-generating modules.

  • Functional network reorganization occurs with changes in the speed of locomotion or changes in gait. This reconfiguration takes places both at the level of rhythm generation and at the level of pattern generation.

  • The exact mechanisms of rhythm generation are not generally understood across phyla but seem to depend on an interplay between active membrane properties and network properties.

  • Proprioception suggests an important role for phase switching during locomotion.

  • The combination of electrophysiological and molecular genetic approaches has revealed details of the organization of large-scale spinal networks in limbed animals in considerably different ways than previous research has suggested and has allowed for comparison with network organization in leg-less animals with more limited numbers of cells in the spinal cord. Although these fundamental motor networks have begun to be decoded, there are still unresolved issues regarding their functional organization.

Abstract

Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait.

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Figure 1: Organization of neuronal control of locomotion in vertebrates.
Figure 2: Multiple left–right coordination circuits.
Figure 3: Organizational and molecular delineation of rhythm-generating circuits.
Figure 4: Multiple levels of flexor–extensor antagonism.
Figure 5: Proprioceptive input directs stance and swing phase transitions.

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Acknowledgements

The work in the Kiehn laboratory is supported by the Swedish Research Council, The European Research Council advanced grant, Ragnar and Torsten Söderbergs Foundation, Karolinska Institutet, NIH and Hjärnfonden. The author thanks colleagues for many inspiring discussions regarding themes discussed in this Review. The author thanks K. Dougherty for reading a previous version of this article.

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PowerPoint slides

Glossary

Gait

A description of the pattern of limb movements. Different gaits have different patterns of movements and are often expressed as a function of the speed of locomotion.

Mesencephalic locomotor region

(MLR). A region in the midbrain where electrical stimulation initiates locomotion. The strength of stimulation regulates the speed of locomotion.

Commissural neurons

(CNs). Excitatory or inhibitory neurons that have axons crossing between the left side and the right side of the nervous system.

Transcription factor

A protein that binds to DNA and controls the transcription of DNA to RNA. Expressed in specific populations of neurons during development.

Monosynaptically restricted trans-synaptic labelling

An anatomical viral-based method in which a fluorescently labelled virus jumps one synapse from a target population of neurons to their immediate presynaptic partners. Used for detailed connectivity studies.

Rhythm-generating neurons

Excitatory neurons that are primarily involved in rhythm generation.

Pacemaker properties

Neuronal membrane properties that endow cells with the capability to produce endogenous bursting.

Renshaw cells

Inhibitory neurons that are excited via recurrent collaterals from motor neurons. They project back to motor neurons and inhibit them. They also inhibit reciprocal Ia interneurons.

Recurrent inhibition

Inhibitory cells that are activated by excitatory cells and that provide inhibition of other cells occasionally including the cell that provided the excitation.

Golgi tendon organs

(GTOs). Force-activated receptors in tendons.

Proprioception

The awareness of body and limb position. Mediated by proprioceptive movement-activated receptors in muscles, tendons and joints.

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Kiehn, O. Decoding the organization of spinal circuits that control locomotion. Nat Rev Neurosci 17, 224–238 (2016). https://doi.org/10.1038/nrn.2016.9

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