Spinal Network Development

Keith T Sillar, University of St. Andrews, Scotland, UK
David L McLean, Northwestern University, Evanston, Illinois, USA

Published online: June 2010

DOI: 10.1002/9780470015902.a0000834.pub2

This article is a review of research into the development of the spinal networks that control rhythmic locomotor movements. By the time they reach adulthood, most animals display a complex repertoire of characteristic motor behaviours that are essential for their survival. One such behaviour is locomotion, which involves rhythmically repeating movements of the body or appendages, produced by the coordinated contractions of different skeletal muscle groups. Muscle contractions are generated by bursts of action potentials in motorneurons (MNs) whose firing patterns are controlled by networks of interneurons that reside principally in the spinal cord and hindbrain. This article provides an overview of current knowledge on the development of the neuronal networks that control locomotion.

Key Concepts:

  • Locomotion in vertebrates involves rhythmic contractions of functionally antagonistic pairs of muscles.
  • The locomotor rhythm is generated by networks of neurons in the central nervous system, often called central pattern generators (CPGs).
  • The neural networks responsible for locomotion arise early in vertebrate development, often before birth or hatching.
  • Locomotor network development precedes the emergence of the behaviours the networks will eventually control.
  • Neural mechanisms for locomotor rhythm generation appear to be similar across a range of species.
  • The basic rhythm is generated by glutamate-mediated excitation and glycine-mediated inhibition.
  • The motor output generated by immature locomotor networks often lacks the flexibility required of adult behaviour.
  • During locomotor network maturation there is a sequence of changes in the properties of and connections between spinal neurons.
  • During development, locomotor networks are progressively influenced by neuromodulatory systems, many of which originate from nuclei in the brainstem.
  • Serotonin released from neurons of the raphe nuclei in the brainstem appears to be a particularly important neuromodulator.
  • The way in which additional components are added sequentially to locomotor networks in different species ensures the motor output matches the development stage-specific behavioural requirements of the host organism.

Keywords: motor control; spinal cord; locomotion; development; rhythm generation; neuromodulation; CPG; neural network; metamorphosis; motorneuron

 References
    Alvarez FJ, Jonas PC, Sapir T et al. (2005) Postnatal phenotype and localization of spinal cord V1 derived interneurons. Journal of Comparetive Neurology 493: 177–192.
    Ben-Ari Y, Gaiarsa JL, Tyzio R and Khazipov R (2007) GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiological Review 87: 1215–1284.
    Borodinsky LN, Root CM, Cronin JA et al. (2004) Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429: 523–530.
    Branchereau P, Morin D, Bonnot A et al. (2000) Development of lumbar rhythmic networks: from embryonic to neonate locomotor-like patterns in the mouse. Brain Research Bulletin 53: 711–718.
    Brown TG (1911) The intrinsic factors in the act of progression in mammals. Proceedings of the Royal Society of London. Series B 84: 308–319.
    Combes D, Merrywest SD, Simmers J and Sillar KT (2004) Developmental segregation of spinal networks driving axial- and hindlimb-based locomotion in metamorphosing Xenopus laevis. Journal of Physiology 559: 17–24.
    Crone SA, Quinlan KA, Zagoraiou L et al. (2008) Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron 60: 70–83.
    Crone SA, Zhong G, Harris-Warrick R and Sharma K (2009) In mice lacking V2a interneurons, gait depends on speed of locomotion. Journal of Neuroscience 29: 7098–7109.
    de Vries JI, Visser GH and Prechtl HF (1982) The emergence of fetal behaviour. I. Qualitative aspects. Early Human Development 7: 301–322.
    Gonzalez-Islas C and Wenner P (2006) Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength. Neuron 49: 563–575.
    Gosgnach S, Lanuza GM, Butt SJ et al. (2006) V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature 440: 215–219.
    Goulding M and Pfaff SL (2005) Development of circuits that generate simple rhythmic behaviors in vertebrates. Current Opinion in Neurobiology 15: 14–20.
    other Grillner S, El Manira A, Kiehn O, Rossignol S and Stein PSG (eds) (2008) Networks in motion. Brain Research Reviews 57: 1–270.
    Hanson MG and Landmesser LT (2003) Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord. Journal of Neuroscience 23: 587–600.
    Hanson MG and Landmesser LT (2006) Increasing the frequency of spontaneous rhythmic activity disrupts pool-specific axon fasciculation and pathfinding of embryonic spinal motoneurons. Journal of Neuroscience 26: 12769–12780.
    Higashijima S, Masino MA, Mandel G and Fetcho JR (2004) Engrailed-1 expression marks a primitive class of inhibitory spinal interneuron. Journal of Neuroscience 24: 5827–5839.
    Jamon M and Clarac F (1998) Early walking in the neuronatal rat: a kinematic study. Behavioural Neuroscience 112: 1218–1228.
    Jean-Xavier C, Mentis GZ, O'Donovan MJ, Cattaert D and Vinay L (2007) Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Proceedings of the National Academy of Sciences of the USA 104: 11477–11482.
    Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Reviews Genetics 1: 20–29.
    book Kiehn O, Hounsgaard J and Sillar KT (1997) "Building blocks in vertebrate central pattern generators". In: Stein PSG, Stuart D, Grillner S and Selverston AI (eds) Neurons, Networks and Motor Behavior, pp. 47–59. Boston: MIT Press.
    Lanuza GM, Gosgnach S, Pierani A, Jessell TM and Goulding M (2004) Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements. Neuron 42: 375–386.
    Li WC, Higashijima S, Parry DM, Roberts A and Soffe SR (2004) Primitive roles for inhibitory interneurons in developing frog spinal cord. Journal of Neuroscience 24: 5840–5848.
    Li WC, Soffe SR, Wolf E and Roberts A (2006) Persistent responses to brief stimuli: feedback excitation among brainstem neurons. Journal of Neuroscience 26: 4026–4035.
    McDearmid JR, Scrymgeour-Wedderburn JF and Sillar KT (1997) Aminergic modulation of glycine release in a spinal network controlling swimming in Xenopus laevis. Journal of Physiology 503(Part 1): 111–117.
    McLean DL, Fan J, Higashijima S, Hale ME and Fetcho JR (2007) A topographic map of recruitment in spinal cord. Nature 446: 71–75.
    McLean DL and Fetcho JR (2009) Spinal interneurons differentiate sequentially from those driving the fastest swimming movemens in larval zebrafish to those driving the slowest ones. Journal of Neuroscience 29: 13566–13577.
    McLean DL, Masino MA, Koh IY, Lindquist WB and Fetcho JR (2008) Continuous shifts in the active set of spinal interneurons during changes in locomotor speed. Nature Neuroscience 11: 1419–1429.
    Nakayama K, Nishimaru H and Kudo N (2002) Basis of changes in left-right coordination of rhythmic motor activity during development in the rat spinal cord. Journal of Neuroscience 22: 10388–10398.
    Nishimaru H, Iizuka M, Ozaki S and Kudo N (1996) Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro. Journal of Physiology 497(part 1): 131–143.
    O'Donovan M, Sernagor E, Sholomenko G et al. (1992) Development of spinal motor networks in the chick embryo. Journal of Experimental Zoology 261: 261–273.
    Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM and Arber S (2009) Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition. Nature 459: 842–846.
    Rauscent A, Einum J, Le Ray D, Simmers J and Combes D (2009) Opposing aminergic modulation of distinct spinal locomotor circuits and their functional coupling during amphibian metamorphosis. Journal of Neuroscience 29: 1163–1174.
    Roberts A, Li WC, Soffe SR and Wolf E (2008) Origin of excitatory drive to a spinal locomotor network. Brain Research Review 57: 22–28.
    Saint-Amant L and Drapeau P (1998) Time course of the development of motor behaviors in the zebrafish embryo. Journal of Neurobiology 37: 622–632.
    Sillar KT (1994) Synaptic specificity: development of locomotor rhythmicity. Current Opinion in Neurobiology 4: 101–107.
    Sillar KT, Simmers AJ and Wedderburn JF (1992) The post-embryonic development of cell properties and synaptic drive underlying locomotor rhythm generation in Xenopus larvae. Proceedings: Biological Sciences 249: 65–70.
    Sillar KT, Woolston AM and Wedderburn JF (1995) Involvement of brainstem serotonergic interneurons in the development of a vertebrate spinal locomotor circuit. Proceedings. Biological Sciences 259: 65–70.
    Soffe SR, Roberts A and Li WC (2009) Defining the excitatory neurons that drive the locomotor rhythm in a simple vertebrate: insights into the origin of reticulospinal control. Journal of Physiology 26: 4026–4035.
    Sun Q and Dale N (1998) Developmental changes in expression of ion currents accompany maturation of locomotor pattern in frog tadpoles. Journal of Physiology 507(part 1): 257–264.
    Vinay L, Brocard F, Pflieger JF, Simeoini-Alias J and Clarac F (2000) Perinatal development of lumbar motoneurons and their inputs in the rat. Brain Research Bulletin 53: 635–647.
    Yang JF, Lamont EV and Pang MY (2005) Split-belt treadmill stepping in infants suggests autonomous pattern generators for the left and right leg in humans. Journal of Neuroscience 25: 6869–6876.
    Zhang HY, Li WC, Heitler WJ and Sillar KT (2009) Electrical coupling synchronises spinal motoneuron activity during swimming in hatchling Xenopus tadpoles. Journal of Physiology 587: 4455–4466.
 Further Reading
    Fetcho JR, Higashijima S and McLean DL (2008) Zebrafish and motor control over the last decade. Brain Research Review 57: 86–93.
    Goulding M (2009) Circuits controlling vertebrate locomotion: moving in a new direction. Nature Reviews Neuroscience 10: 507–518.
    Grillner S (2006) Biological pattern generation: the cellular and computational logic of networks in motion. Neuron 52: 751–766.
    Grillner S and Jessell TM (2009) Measured motion: searching for simplicity in spinal locomotor networks. Current Opinion of Neurobiology 19: 572–586.
    Kiehn O (2006) Locomotor circuits in the mammalian spinal cord. Annual Review of Neuroscience 29: 230–279.
    McLean DL and Fetcho JR (2008) Using imaging and genetics in zebrafish to study developing spinal circuits in vivo. Developmental Neurobiology 68: 817–834.
    Sillar KT, Combes D, Ramanathan S, Molinari M and Simmers J (2008) Neuromodulation and developmental plasticity in the locomotor system of anuran amphibians during metamorphosis. Brain Research Review 57: 94–102.

Related Sub-Topics:

Organisation of the Nervous System | Nervous System Development | Neural Networks and Behaviour | Development of Vertebrate Nervous System
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Article Title: Spinal Network Development
 
How to Cite close
Sillar, Keith T, and McLean, David L(Jun 2010) Spinal Network Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000834.pub2]