The motor infrastructure: from ion channels to neuronal networks

Key Points

  • The motor system is the only external output channel of the brain. Various networks at different levels of the nervous system coordinate a multitude of motor patterns, such as eye or hand movements, or those that underlie respiration, locomotion or posture. Together, these networks provide a 'motor infrastructure' that is used by the nervous system to generate the movement repertoire of an organism or a species. Some networks are present at birth, whereas others mature during development to become modified and perfected through learning.

  • Whereas the presence of networks coordinating movements has long been established, the intrinsic function of these networks in vertebrates has only recently started to be unravelled. The lamprey locomotor network is one of the few vertebrate networks that is well understood.

  • The basic burst-generating core of the network consists of populations of glutamatergic excitatory interneurons, which excite each other through NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. They also activate a group of motor neurons and glycinergic neurons that inhibit antagonistic burst-generating populations. This organization results in alternating activity in groups of motor neurons.

  • Burst generation and termination in a population is determined by the background excitatory drive and the different ion channel subtypes that are expressed. Ca2+- and voltage-activated ion channels, such as Ca2+-dependent K+ channels, NMDA receptors, Ca2+ channel subtypes and K+ channels (Kv3), have an important role. A sensory overlay can also influence burst onset and termination. Local inhibitory interneurons with ipsilateral axons are not required for burst generation but might, under some conditions, influence burst termination.

  • G-protein-coupled receptors contribute to the fine tuning of the network activity, although they need not be activated for burst generation to occur. Some modulator/transmitter neurons are activated as part of the network operation (acting through 5-HT (5-hydroxytryptamine, serotonin), GABA (γ-aminobutyric acid) and metabotropic glutamate receptors), whereas others provide an independent input (including 5-HT, cholecystokinin and peptide YY(PYY)). They act by modulating different subtypes of ion channels in the soma, or by modifying synaptic efficacy at the pre- or postsynaptic level. For example, tachykinins can produce short or long-term changes.

  • The detailed analysis of the network has been possible through extensive modelling at the ion channel, cell, network and neuromechanical levels in close interaction with the experimental analyses.

  • Vertebrate locomotion, whether swimming, walking or flying, requires a complex motor pattern involving hundreds of muscles, controlled through brainstem command centres that regulate the level of activity in spinal cord networks, which generate the detailed pattern of muscle activity. The neural control system has been remarkably well conserved through vertebrate evolution.

Abstract

The vertebrate motor system is equipped with a number of neuronal networks that underlie different patterns of behaviour, from simple protective reflexes to complex movements. The current challenge is to understand the intrinsic function of these networks: that is, the cellular basis of motor behaviour. In one vertebrate model system, the lamprey, it has been possible to make the connection between different subtypes of ion channels and transmitters and their roles at the cellular and network levels. It is therefore possible to link the role of certain genes or molecules to motor behaviour in this system.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The motor infrastructure.
Figure 2: Similarities of locomotor pattern generation in an intact lamprey and an isolated spinal cord.
Figure 3: Locomotor network of the lamprey.
Figure 4: The roles of the slow afterhyperpolarization (sAHP) and KCa channels at the single cell and network level.
Figure 5: Factors controlling burst onset and termination.
Figure 6: Modelling the lamprey locomotor network.
Figure 7: Effects on the central pattern generator (CPG) of sensory input from stretch receptors activated during the movement.
Figure 8: Intersegmental coordination in the lamprey.

References

  1. 1

    Eccles, J. C. & Gibson, W. C. Sherrington: His Life and Thought (Berlin, Springer, 1979).

  2. 2

    Grillner, S. in Fundamental Neuroscience (eds. Zigmond, M. J., Bloom, F. E., Landis, S. C., Roberts, J. L. & Squire, L. R.) 755–767 (Academic, San Diego, 2002). A general review of the motor system, from simple to complex.

  3. 3

    Nieuwenhuys, R., Donkelaar, H. J. & Nicholson, C. The Central Nervous System of Vertebrates Vol. 1 (Springer, Berlin, 1998).

  4. 4

    Delcomyn, F. Motor activity during searching and walking movements of cockroach legs. J. Exp. Biol. 133, 111–120 (1987).

  5. 5

    von Euler, C. The contribution of sensory inputs to the pattern generation of breathing. Can. J. Physiol. Pharmacol. 59, 700–706 (1981).

  6. 6

    Grillner, S. Neural networks for vertebrate locomotion. Sci. Am. 274, 64–69 (1996).

  7. 7

    Grillner, S. Neurobiological bases of rhythmic motor acts in vertebrates. Science 228, 143–149 (1985).

  8. 8

    Grillner, S. in Handbook of Physiology, Section 1. The Nervous System II. Motor Control (ed. Brooks, V. B.) 1179–1236 (American Physiological Society, Waverly, Maryland, 1981).

  9. 9

    Grillner, S. Locomotion in vertebrates: central mechanisms and reflex interaction. Physiol. Rev. 55, 247–304 (1975).

  10. 10

    Isa, T. Intrinsic processing in the mammalian superior colliculus. Curr. Opin. Neurobiol. 12, 668–677 (2002). A brief review of the network underlying saccade generation.

  11. 11

    Sparks, D. L. The brainstem control of saccadic eye movements. Nature Rev. Neurosci. 3, 952–964 (2002).

  12. 12

    Darwin, C. The Expression of the Emotions in Man and Animals (Univ. Chicago Press (1965), Chicago and London, 1872). The classic description of innate motor patterns.

  13. 13

    Russell, J. & Bullock, M. Multidimensional scaling of emotional facial expressions: similarity from preschoolers to adults. J. Pers. Soc. Psychol. 48, 1290–1298 (1985).

  14. 14

    Ito, M. The molecular organization of cerebellar long-term depression. Nature Rev. Neurosci. 3, 896–902 (2002).

  15. 15

    Jog, M. S., Kubota, Y., Connolly, C. I., Hillegaart, V. & Graybiel, A. M. Building neural representations of habits. Science 286, 1745–1749 (1999).

  16. 16

    Grillner, S. Recombination of motor pattern generators. Simple neuronal networks combine to produce complex versatile motor patterns. Curr. Biol. 1, 231–233 (1991).

  17. 17

    Grillner, S. & Wallén, P. in Brain Mechanisms for the Integration of Posture and Movement (eds Mori, S., Stuart, D. G. & Wiesendanger, M.) (Elsevier, Amsterdam, in the press).

  18. 18

    Duysens, J. & Pearson, K. G. Inhibition of flexor burst generation by loading ankle extensor muscles in walking cats. Brain Res. 187, 321–332 (1980).

  19. 19

    Grillner, S. & Rossignol, S. On the initiation of the swing phase of locomotion in chronic spinal cats. Brain Res. 146, 269–277 (1978).

  20. 20

    Lam, T. & Pearson, K. G. The role of proprioceptive feedback in the regulation and adaptation of locomotor activity. Adv. Exp. Med. Biol. 508, 343–355 (2002).

  21. 21

    Stein, R. B., Misiaszek, J. E. & Pearson, K. G. Functional role of muscle reflexes for force generation in the decerebrate walking cat. J. Physiol. (Lond.) 525, 781–791 (2000).

  22. 22

    Massion, J. Postural control system. Curr. Opin. Neurobiol. 4, 877–887 (1994).

  23. 23

    Grillner, S. The role of muscle stiffness in meeting the changing postural and locomotor requirements for force development by the ankle extensors. Acta Physiol. Scand. 86, 92–108 (1972).

  24. 24

    Orlovsky, G. N., Deliagina, T. G. & Grillner, S. Neuronal Control of Locomotion. From Mollusc to Man (Oxford Univ. Press, New York, 1999). A comparative review of locomotor control systems throughout the animal kingdom.

  25. 25

    Shik, M. L. & Orlovsky, G. N. Neurophysiology of locomotor automatism. Physiol. Rev. 56, 465–501 (1976).

  26. 26

    von Holst, E. Über relative Koordination bei Saugern und beim Menschen. Pfluegers Archiv. 240, 44–49 (1938).

  27. 27

    Wiersma, C. A. G. & Ikeda, K. Interneurons commanding swimmeret movements in the crayfish, Procambarus clarkii (Girard). Comp. Biochem. Physiol. 12, 509–525 (1964).

  28. 28

    Kiehn, O. & Kjaerulff, O. Distribution of central pattern generators for rhythmic motor outputs in the spinal cord of limbed vertebrates. Ann. NY Acad. Sci. 860, 110–129 (1998).

  29. 29

    Butt, S. J., Harris-Warrick, R. M. & Kiehn, O. Firing properties of identified interneuron populations in the mammalian hindlimb central pattern generator. J. Neurosci. 22, 9961–9971 (2002). An analysis of interneurons in the rodent locomotor network.

  30. 30

    Kiehn, O. & Tresch, M. C. Gap junctions and motor behavior. Trends Neurosci. 25, 108–115 (2002).

  31. 31

    Vinay, L., Brocard, F. & Clarac, F. Differential maturation of motoneurons innervating ankle flexor and extensor muscles in the neonatal rat. Eur. J. Neurosci. 12, 4562–4566 (2000).

  32. 32

    Pflieger, J. F., Clarac, F. & Vinay, L. Postural modifications and neuronal excitability changes induced by a short-term serotonin depletion during neonatal development in the rat. J. Neurosci. 22, 5108–5117 (2002). A study of developmental changes in the network that controls locomotion.

  33. 33

    Roberts, A., Tunstall, M. J. & Wolf, E. Properties of networks controlling locomotion and significance of voltage dependency of NMDA channels: stimulation study of rhythm generation sustained by positive feedback. J. Neurophysiol. 73, 485–495 (1995).

  34. 34

    Sillar, K. T., Woolston, A. M. & Wedderburn, J. F. Involvement of brainstem serotonergic interneurons in the development of a vertebrate spinal locomotor circuit. Proc. R. Soc. Lond. B. 259, 65–70 (1995).

  35. 35

    Tunstall, M. J., Roberts, A. & Soffe, S. R. Modelling inter-segmental coordination of neuronal oscillators: synaptic mechanisms for uni-directional coupling during swimming in Xenopus tadpoles. J. Comput. Neurosci. 13, 143–158 (2002).

  36. 36

    Dale, N. & Kuenzi, F. M. Ion channels and the control of swimming in the Xenopus embryo. Prog. Neurobiol. 53, 729–756 (1997). A review of the intrinsic function of the locomotor network in the developing amphibian nervous system.

  37. 37

    Grillner, S. & Wallen, P. Cellular bases of a vertebrate locomotor system — steering, intersegmental and segmental co-ordination and sensory control. Brain Res. Brain Res. Rev. 40, 92–106 (2002).

  38. 38

    Grillner, S., Georgopoulos, A. P. & Jordan, L. in Neurons, Networks and Motor Behavior (eds Stein, P. S. G., Grillner, S., Selverston, A. I. & Stuart, D. G.) 3–19 (MIT Press, Cambridge, Massachusetts, 1997). A discussion of the different supraspinal systems that contribute to vertebrate locomotor control.

  39. 39

    Sirota, M. G., Di Prisco, G. V. & Dubuc, R. Stimulation of the mesencephalic locomotor region elicits controlled swimming in semi-intact lampreys. Eur. J. Neurosci. 12, 4081–4092 (2000).

  40. 40

    Di Prisco, G. V., Pearlstein, E., Le Ray, D., Robitaille, R. & Dubuc, R. A cellular mechanism for the transformation of a sensory input into a motor command. J. Neurosci. 20, 8169–8176 (2000). A study of the role of plateau potentials in the reticulospinal neurons that mediate locomotor drive.

  41. 41

    Fedirchuk, B., Nielsen, J., Petersen, N. & Hultborn, H. Pharmacologically evoked fictive motor patterns in the acutely spinalized marmoset monkey (Callithrix jacchus). Exp. Brain Res. 122, 351–361 (1998).

  42. 42

    Cangiano, L. & Grillner, S. Fast and slow locomotor burst generation in the hemi–spinal cord of the lamprey. J. Neurophysiol. 89, 2931–2942 (2003) A demonstration of locomotor burst generation in hemisegments, and without inhibition.

  43. 43

    Buchanan, J. T. Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. J. Neurophysiol. 81, 2037–2045 (1999).

  44. 44

    Cangiano, L. & Grillner, S. Fast and slow locomotor burst generation in the hemi-spinal cord of the lamprey. Soc. Neurosci. Abstr. 28, 65.10 (2002).

  45. 45

    Cohen, A. H. & Harris-Warrick, R. M. Strychnine eliminates alternating motor output during fictive locomotion in the lamprey. Brain Res. 293, 164–167 (1984).

  46. 46

    Grillner, S. & Wallen, P. Does the central pattern generator for locomotion in lamprey depend on glycine inhibition? Acta Physiol. Scand. 110, 103–105 (1980).

  47. 47

    Buchanan, J. T. Identification of interneurons with contralateral, caudal axons in the lamprey spinal cord: synaptic interactions and morphology. J. Neurophysiol. 47, 961–975 (1982).

  48. 48

    Buchanan, J. T. & Grillner, S. Newly identified 'glutamate interneurons' and their role in locomotion in the lamprey spinal cord. Science 236, 312–314 (1987). The original description of spinal locomotor connectivity.

  49. 49

    Parker, D. & Grillner, S. Activity-dependent metaplasticity of inhibitory and excitatory synaptic transmission in the lamprey spinal cord locomotor network. J. Neurosci. 19, 1647–1656 (1999).

  50. 50

    Parker, D. & Grillner, S. The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord. Eur. J. Neurosci. 12, 2135–2146 (2000).

  51. 51

    Ohta, Y., Dubuc, R. & Grillner, S. A new population of neurons with crossed axons in the lamprey spinal cord. Brain Res. 564, 143–148 (1991).

  52. 52

    Buchanan, J. T. & Grillner, S. A new class of small inhibitory interneurones in the lamprey spinal cord. Brain Res. 438, 404–407 (1988).

  53. 53

    Ohta, Y. & Grillner, S. Monosynaptic excitatory amino acid transmission from the posterior rhombencephalic reticular nucleus to spinal neurons involved in the control of locomotion in lamprey. J. Neurophysiol. 62, 1079–1089 (1989).

  54. 54

    Stein, P. S. Central pattern generators and interphyletic awareness. Prog. Brain Res. 123, 259–271 (1999).

  55. 55

    O'Donovan, M. J., Wenner, P., Chub, N., Tabak, J. & Rinzel, J. Mechanisms of spontaneous activity in the developing spinal cord and their relevance to locomotion. Ann. NY Acad. Sci. 860, 130–141 (1998).

  56. 56

    Drapeau, P. et al. Development of the locomotor network in zebrafish. Prog. Neurobiol. 68, 85–111 (2002). A review of recent studies of the developing zebrafish locomotor system.

  57. 57

    Rossignol, S. et al. Pharmacological activation and modulation of the central pattern generator for locomotion in the cat. Ann. NY Acad. Sci. 860, 346–359 (1998).

  58. 58

    Perrins, R. & Roberts, A. Cholinergic and electrical synapses between synergistic spinal motoneurones in the Xenopus laevis embryo. J. Physiol. (Lond.) 485, 135–144 (1995).

  59. 59

    Placas, P. G. & Buchanan, J. T. Endogenous release of acetylcholine modulates the locomotor network of the lamprey spinal cord. Soc. Neurosci. Abstr. 28, 270.10 (2002).

  60. 60

    Perrins, R. & Roberts, A. Cholinergic contribution to excitation in a spinal locomotor central pattern generator in Xenopus embryos. J. Neurophysiol. 73, 1013–1019 (1995).

  61. 61

    Tegner, J. & Grillner, S. Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. J. Neurophysiol. 81, 1318–1329 (1999).

  62. 62

    Tegner, J., Matsushima, T., El Manira, A. & Grillner, S. The spinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors. J. Neurophysiol. 69, 647–657 (1993).

  63. 63

    Schmitt, D. E., Hill, R. H. & Grillner, S. A GABAA activation contributes to the locomotor pattern generation by slowing the locomotor rhythm in lamprey. Soc. Neurosci. Abstr. 28, 65.7 (2002).

  64. 64

    Reith, C. A. & Sillar, K. T. Development and role of GABAA receptor-mediated synaptic potentials during swimming in postembryonic Xenopus laevis tadpoles. J. Neurophysiol. 82, 3175–3187 (1999).

  65. 65

    El Manira, A., Tegner, J. & Grillner, S. Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey. J. Neurophysiol. 72, 1852–1861 (1994). A description of the role of calcium-dependent potassium channels in the locomotor network.

  66. 66

    Cangiano, L., Wallen, P. & Grillner, S. Role of apamin-sensitive KCa channels for reticulospinal synaptic transmission to motoneuron and for the afterhyperpolarization. J. Neurophysiol. 88, 289–299 (2002).

  67. 67

    Wallén, P., Hess, D., El Manira, A. & Grillner, S. A slow non-Ca2+-dependent afterhyperpolarization in lamprey neurons. Soc. Neurosci. Abstr. 28, 46.9 (2002).

  68. 68

    Wikstrom, M. A. & El Manira, A. Calcium influx through N- and P/Q-type channels activate apamin-sensitive calcium-dependent potassium channels generating the late afterhyperpolarization in lamprey spinal neurons. Eur. J. Neurosci. 10, 1528–1532 (1998).

  69. 69

    Schotland, J. et al. Control of lamprey locomotor neurons by colocalized monoamine transmitters. Nature 374, 266–268 (1995).

  70. 70

    Matsushima, T., Tegner, J., Hill, R. H. & Grillner, S. GABAB receptor activation causes a depression of low- and high-voltage-activated Ca2+ currents, postinhibitory rebound, and postspike afterhyperpolarization in lamprey neurons. J. Neurophysiol. 70, 2606–2619 (1993).

  71. 71

    Krieger, P., Buschges, A. & El Manira, A. Calcium channels involved in synaptic transmission from reticulospinal axons in lamprey. J. Neurophysiol. 81, 1699–1705 (1999).

  72. 72

    Grillner, S., Wallen, P., Hill, R., Cangiano, L. & El Manira, A. Ion channels of importance for the locomotor pattern generation in the lamprey brainstem-spinal cord. J. Physiol. (Lond.) 533, 23–30 (2001). A review of ion channels that are important for pattern generation in the lamprey.

  73. 73

    Buschges, A., Wikstrom, M. A., Grillner, S. & El Manira, A. Roles of high-voltage-activated calcium channel subtypes in a vertebrate spinal locomotor network. J. Neurophysiol. 84, 2758–2766 (2000).

  74. 74

    Matsushima, T. & Grillner, S. Neural mechanisms of intersegmental coordination in lamprey: local excitability changes modify the phase coupling along the spinal cord. J. Neurophysiol. 67, 373–88 (1992).

  75. 75

    Lamotte d´Incamps, B., Hess, D. & El Manira, A. A-type potassium current limits synaptic transmission by normalizing presynaptic spike waveform and calcium influx. Soc. Neurosci. Abstr. 27, 384.8 (2001).

  76. 76

    Hess, D. & El Manira, A. Characterization of a high-voltage-activated IA current with a role in spike timing and locomotor pattern generation. Proc. Natl Acad. Sci. USA 98, 5276–5281 (2001). A study on the role of Kv3.4-like channels in locomotor pattern generation.

  77. 77

    Hu, G. Y., Biro, Z., Hill, R. H. & Grillner, S. Intracellular QX-314 causes depression of membrane potential oscillations in lamprey spinal neurons during fictive locomotion. J. Neurophysiol. 87, 2676–2683 (2002). A demonstration of the potentiation of locomotor drive synaptic potentials by soma-dendritic Na+ channels.

  78. 78

    Tegner, J., Hellgren-Kotaleski, J., Lansner, A. & Grillner, S. Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment. J. Neurophysiol. 77, 1795–1812 (1997).

  79. 79

    Wallen, P. & Grillner, S. N-methyl-D-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey. J. Neurosci. 7, 2745–2755 (1987).

  80. 80

    Bacskai, B. J., Wallen, P., Lev-Ram, V., Grillner, S. & Tsien, R. Y. Activity-related calcium dynamics in lamprey motoneurons as revealed by video-rate confocal microscopy. Neuron 14, 19–28 (1995).

  81. 81

    Guertin, P. A. & Hounsgaard, J. NMDA-induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles. J. Neurophysiol. 80, 3380–3382 (1998).

  82. 82

    El Manira, A., Parker, D., Krieger, P., Wikstrom, M. & Grillner, S. in Presynaptic Inhibition and Neural Control (eds Rudomin, P., Romo, R. & Mendell, L.) 329–348 (Oxford Univ. Press, 1998). An overview of presynaptic modulation in various transmitter systems.

  83. 83

    El Manira, A., Tegner, J. & Grillner, S. Locomotor-related presynaptic modulation of primary afferents in the lamprey. Eur. J. Neurosci. 9, 696–705 (1997).

  84. 84

    Alford, S., Christenson, J. & Grillner, S. Presynaptic GABAA and GABAB receptor-mediated phasic modulation in axons of spinal motor interneurons. Eur. J. Neurosci. 3, 107–117 (1991).

  85. 85

    Parker, D. & Grillner, S. Long-lasting substance-P-mediated modulation of NMDA-induced rhythmic activity in the lamprey locomotor network involves separate RNA- and protein-synthesis-dependent stages. Eur. J. Neurosci. 11, 1515–1522 (1999).

  86. 86

    Parker, D. Presynaptic and interactive peptidergic modulation of reticulospinal synaptic inputs in the lamprey. J. Neurophysiol. 83, 2497–2507 (2000).

  87. 87

    Ekeberg, O. et al. A computer based model for realistic simulations of neural networks. I. The single neuron and synaptic interaction. Biol. Cybern. 65, 81–90 (1991).

  88. 88

    Ekeberg, Ö., Lansner, A. & Grillner, S. The neural control of fish swimming studied through numerical simulations. Adapt. Behav. 3, 363–384 (1995).

  89. 89

    Hellgren, J., Grillner, S. & Lansner, A. Computer simulation of the segmental neural network generating locomotion in lamprey by using populations of network interneurons. Biol. Cybern. 68, 1–13 (1992).

  90. 90

    Kozlov, A. K. et al. Mechanisms for lateral turns in lamprey in response to descending unilateral commands: a modeling study. Biol. Cybern. 86, 1–14 (2002).

  91. 91

    Brodin, L. et al. Computer simulations of N-methyl-D-aspartate receptor-induced membrane properties in a neuron model. J. Neurophysiol. 66, 473–484 (1991).

  92. 92

    Zhang, W. & Grillner, S. The spinal 5-HT system contributes to the generation of fictive locomotion in lamprey. Brain Res. 879, 188–192 (2000).

  93. 93

    Svensson, E., Grillner, S., Kristensson, K. & Hill, R. H. Midline modulator neurons are rhythmically active during fictive locomotion in the lamprey spinal cord. Soc. Neurosci. Abstr. 28, 65.9 (2002).

  94. 94

    Wikstrom, M., Hill, R., Hellgren, J. & Grillner, S. The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors. Brain Res. 678, 191–199 (1995).

  95. 95

    Schmidt, B. J. & Jordan, L. M. The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord. Brain Res. Bull. 53, 689–710 (2000).

  96. 96

    Kettunen, P., Hallén, K. & El Manira, A. Release of endogenous cannabinoids by group I mGluR activation modulates the locomotor rhythm in the lamprey. Soc. Neurosci. Abstr. 28, 167.5 (2002).

  97. 97

    Krieger, P., Hellgren-Kotaleski, J., Kettunen, P. & El Manira, A. J. Interaction between metabotropic and ionotropic glutamate receptors regulates neuronal network activity. J. Neurosci. 20, 5382–5391 (2000). An elegant study of the contribution of metabotropic glutamate receptors to cell and network activity.

  98. 98

    Hess, D., Kettunen, P., Krieger, P. & El Manira, A. Pharmacology and mechanisms of group I mGluR-mediated effects in lamprey spinal cord neurons. Soc. Neurosci. Abstr. 27, 705.5 (2001).

  99. 99

    Wallen, P. et al. Effects of 5-hydroxytryptamine on the afterhyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons. J. Neurophysiol. 61, 759–768 (1989).

  100. 100

    Svensson, E., Dewael, Y., Hill, R. H. & Grillner, S. 5-HT inhibits N-type calcium channels in lamprey spinal neurons. Soc. Neurosci. Abstr. 27, 934.14 (2001).

  101. 101

    Parker, D., Zhang, W. & Grillner, S. Substance P modulates NMDA responses and causes long-term protein synthesis-dependent modulation of the lamprey locomotor network. J. Neurosci. 18, 4800–4813 (1998). A demonstration of the long-lasting (24 h) effects that brief (10 min) applications of tachykinins can exert on the locomotor network.

  102. 102

    Harris-Warrick, R. M. & Cohen, A. H. Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord. J. Exp. Biol. 116, 27–46 (1985).

  103. 103

    McLean, D. L. & Sillar, K. T. Nitric oxide selectively tunes inhibitory synapses to modulate vertebrate locomotion. J. Neurosci. 22, 4175–4184 (2002). A study of the role of nitric oxide in the control of the tadpole locomotor network.

  104. 104

    Dale, N. & Gilday, D. Regulation of rhythmic movements by purinergic neurotransmitters in frog embryos. Nature 383, 259–263 (1996).

  105. 105

    Van Dongen, P. A. et al. Immunohistochemical and chromatographic studies of peptides with tachykinin-like immunoreactivity in the central nervous system of the lamprey. Peptides 7, 297–313 (1986).

  106. 106

    Dale, N. & Kuenzi, F. Ionic currents, transmitters and models of motor pattern generators. Curr. Opin. Neurobiol. 7, 790–796 (1997).

  107. 107

    Grillner, S., Williams, T. & Lagerback, P. A. The edge cell, a possible intraspinal mechanoreceptor. Science 223, 500–503 (1984).

  108. 108

    Di Prisco, G. V., Wallen, P. & Grillner, S. Synaptic effects of intraspinal stretch receptor neurons mediating movement-related feedback during locomotion. Brain Res. 530, 161–166 (1990).

  109. 109

    Vinay, L., Barthe, J. Y. & Grillner, S. Central modulation of stretch receptor neurons during fictive locomotion in lamprey. J. Neurophysiol. 76, 1224–1235 (1996).

  110. 110

    Grillner, S. On the generation of locomotion in the spinal dogfish. Exp. Brain Res. 20, 459–470 (1974). The original description of the intersegmental phase lag in fish swimming.

  111. 111

    Grillner, S. & Kashin, S. in Neural Control of Locomotion Vol. 18 (eds Herman, R. M., Grillner, S., Stein, P. S. G. & Stuart, D. G.) 181–202 (Plenum, New York, 1976).

  112. 112

    Wallen, P. & Williams, T. L. Fictive locomotion in the lamprey spinal cord in vitro compared with swimming in the intact and spinal animal. J. Physiol. (Lond.) 347, 225–239 (1984).

  113. 113

    McClellan, A. D. & Hagevik, A. Coordination of spinal locomotor activity in the lamprey: long-distance coupling of spinal oscillators. Exp. Brain Res. 126, 93–108 (1999).

  114. 114

    Cohen, A. H. et al. Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion. Trends Neurosci. 15, 434–438 (1992).

  115. 115

    Jung, R., Kiemel, T. & Cohen, A. H. Dynamic behavior of a neural network model of locomotor control in the lamprey. J. Neurophysiol. 75, 1074–1086 (1996).

  116. 116

    Fagerstedt, P. & Ullen, F. Lateral turns in the lamprey. I. Patterns of motoneuron activity. J. Neurophysiol. 86, 2246–2256 (2001).

  117. 117

    Deliagina, T. G., Zelenin, P. V., Fagerstedt, P., Grillner, S. & Orlovsky, G. N. Activity of reticulospinal neurons during locomotion in the freely behaving lamprey. J. Neurophysiol. 83, 853–863 (2000).

  118. 118

    Deliagina, T. G. & Orlovsky, G. N. Comparative neurobiology of postural control. Curr. Opin. Neurobiol. 12, 652–657 (2002). A novel comparative analysis of the postural control system.

  119. 119

    Deliagina, T. G., Orlovsky, G. N., Grillner, S. & Wallen, P. Vestibular control of swimming in lamprey. II. Characteristics of spatial sensitivity of reticulospinal neurons. Exp. Brain Res. 90, 489–498 (1992).

  120. 120

    Ullen, F., Deliagina, T. G., Orlovsky, G. N. & Grillner, S. Visual pathways for postural control and negative phototaxis in lamprey. J. Neurophysiol. 78, 960–976 (1997).

  121. 121

    Ekeberg, O. & Grillner, S. Simulations of neuromuscular control in lamprey swimming. Phil. Trans. R Soc. Lond. B 354, 895–902 (1999). A simulation of lamprey locomotor movements based on a biologically realistic network.

  122. 122

    Kotaleski, J. H., Grillner, S. & Lansner, A. Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey. I. Segmental oscillations dependent on reciprocal inhibition. Biol. Cybern. 81, 317–330 (1999).

  123. 123

    Kotaleski, J. H., Lansner, A. & Grillner, S. Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey. II. Hemisegmental oscillations produced by mutually coupled excitatory neurons. Biol. Cybern. 81, 299–315 (1999).

  124. 124

    Bem, T., Cabelguen, J. M., Ekeberg, O. & Grillner, S. From swimming to walking: a single basic network for two different behaviors. Biol. Cybern. 88, 79–90 (2003).

  125. 125

    Dale, N. Coordinated motor activity in simulated spinal networks emerges from simple biologically plausible rules of connectivity. J. Comput. Neurosci. 14, 55–70 (2003).

  126. 126

    Pombal, M. A., El Manira, A. & Grillner, S. Afferents of the lamprey striatum with special reference to the dopaminergic system: a combined tracing and immunohistochemical study. J. Comp. Neurol. 386, 71–91 (1997).

  127. 127

    Pombal, M. A., El Manira, A. & Grillner, S. Organization of the lamprey striatum — transmitters and projections. Brain Res. 766, 249–254 (1997).

  128. 128

    El Manira, A., Pombal, M. A. & Grillner, S. Diencephalic projection to reticulospinal neurons involved in the initiation of locomotion in adult lampreys Lampetra fluviatilis. J. Comp. Neurol. 389, 603–616 (1997).

  129. 129

    Swanson, L. W., Mogenson, G. J., Gerfen, C. R. & Robinson, P. Evidence for a projection from the lateral preoptic area and substantia innominata to the 'mesencephalic locomotor region' in the rat. Brain Res. 295, 161–178 (1984).

  130. 130

    Mogensen, G. J. in Neurobiological Basis of Human Locomotion (ed. Shimamura, M.) 33–44 (Japan Sci. Soc. Press, Tokyo, 1991). A review of the locomotor activation from the nucleus accumbens through the mesopontine locomotor area to the spinal cord in rodents.

  131. 131

    Grillner, S. et al. The intrinsic function of a motor system — from ion channels to networks and behavior. Brain Res. 886, 224–236 (2000).

  132. 132

    Nusbaum, M. P., Blitz, D. M., Swensen, A. M., Wood, D. & Marder, E. The roles of co-transmission in neural network modulation. Trends Neurosci. 24, 146–154 (2001).

  133. 133

    Selverston, A. What invertebrate circuits have taught us about the brain. Brain Res. Bull. 50, 439–440 (1999).

  134. 134

    Katz, P. S. & Harris-Warrick, R. M. The evolution of neuronal circuits underlying species-specific behavior. Curr. Opin. Neurobiol. 9, 628–633 (1999).

  135. 135

    Hill, A. A., Lu, J., Masino, M. A., Olsen, O. H. & Calabrese, R. L. A model of a segmental oscillator in the leech heartbeat neuronal network. J. Comput. Neurosci. 10, 281–302 (2001).

  136. 136

    Kristan, W. B. Jr, Eisenhart, F. J., Johnson, L. A. & French, K. A. Development of neuronal circuits and behaviors in the medicinal leech. Brain Res. Bull. 53, 561–570 (2000).

  137. 137

    Deliagina, T. G., Arshavsky, Y. I. & Orlovsky, G. N. Control of spatial orientation in a mollusc. Nature 393,172–175 (1998).

  138. 138

    Forssberg, H., Grillner, S. & Halbertsma, J. The locomotion of the low spinal cat. I. Coordination within a hindlimb. Acta Physiol. Scand. 108, 269–281 (1980). The first description of well coordinated locomotor movements and EMG pattern in a spinal animal.

  139. 139

    Edgerton, V. R. et al. Retraining the injured spinal cord. J. Physiol. (Lond.) 533, 15–22 (2001). An elegant study that reveals the plasticity of the postural and locomotor systems in spinal animals.

  140. 140

    Edgerton, V. R. & Roy, R. R. Paralysis recovery in humans and model systems. Curr. Opin. Neurobiol. 12, 658–667 (2002).

  141. 141

    Forssberg, H. & Grillner, S. The locomotion of the acute spinal cat injected with clonidine i.v. Brain Res. 50, 184–186 (1973).

  142. 142

    Rossignol, S. et al. The cat model of spinal injury. Prog. Brain Res. 137, 151–168 (2002). A review of the well studied cat model system for spinal injury.

  143. 143

    Tillakaratne, N. J. et al. Use-dependent modulation of inhibitory capacity in the feline lumbar spinal cord. J. Neurosci. 22, 3130–3143 (2002).

  144. 144

    Orsal, D. et al. Locomotor recovery in chronic spinal rat: long-term pharmacological treatment or transplantation of embryonic neurons? Prog. Brain Res. 137, 213–230 (2002). A review of the effect of aminergic transplants in chronic spinal animals.

  145. 145

    Barbeau, H., Fung, J., Leroux, A. & Ladouceur, M. A review of the adaptability and recovery of locomotion after spinal cord injury. Prog. Brain Res. 137, 9–25 (2002).

  146. 146

    Barbeau, H., Ladouceur, M., Norman, K. E., Pepin, A. & Leroux, A. Walking after spinal cord injury: evaluation, treatment, and functional recovery. Arch. Phys. Med. Rehabil. 80, 225–235 (1999).

  147. 147

    Behrman, A. L. & Harkema, S. J. Locomotor training after human spinal cord injury: a series of case studies. Phys. Ther. 80, 688–700 (2000).

  148. 148

    Dietz, V. Do human bipeds use quadrupedal coordination? Trends Neurosci. 25, 462–467 (2002).

  149. 149

    Dietz, V. Proprioception and locomotor disorders. Nature Rev. Neurosci. 3, 781–790 (2002).

  150. 150

    Dietz, V., Muller, R. & Colombo, G. Locomotor activity in spinal man: significance of afferent input from joint and load receptors. Brain 125, 2626–2634 (2002).

  151. 151

    Dietz, V., Wirz, M., Colombo, G. & Curt, A. Locomotor capacity and recovery of spinal cord function in paraplegic patients: a clinical and electrophysiological evaluation. Electroencephalogr. Clin. Neurophysiol. 109, 140–153 (1998).

  152. 152

    Duysens, J. Human gait as a step in evolution. Brain 125, 2589–2590 (2002).

  153. 153

    Harkema, S. J. Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking. Neuroscientist 7, 455–468 (2001). An evaluation of treadmill training for paralysed patients with spinal cord injury.

  154. 154

    Wernig, A., Muller, S., Nanassy, A. & Cagol, E. Laufband therapy based on 'rules of spinal locomotion' is effective in spinal cord injured persons. Eur. J. Neurosci. 7, 823–829 (1995). An initial report of the beneficial effect of treadmill training on patients with spinal cord injury.

  155. 155

    Wernig, A., Nanassy, A. & Muller, S. Maintenance of locomotor abilities following Laufband (treadmill) therapy in para- and tetraplegic persons: follow-up studies. Spinal Cord 36, 744–749 (1998).

  156. 156

    Grillner, S. et al. Neural networks that coordinate locomotion and body orientation. Trends Neurosci. 18, 270–279 (1995).

Download references

Acknowledgements

I would like to acknowledge The Swedish Research Council, European Union and the Wallenberg Foundations for continuous support, and P. Wallén, A. El Manira and R. Hill for critical reading of the manuscript and for a stimulating and creative interaction over many years.

Author information

Affiliations

Authors

Related links

Related links

FURTHER INFORMATION

Encyclopedia of Life Sciences

central pattern generators

motor neurons and spinal control of movement

motor system organization

Glossary

CENTRAL PATTERN GENERATOR

A neural circuit that produces patterns of behaviour independently of sensory input, for instance the pattern of activity in different motor neurons that results in respiration or locomotion.

SACCADIC EYE MOVEMENTS

A rapid eye movement (with speeds of up to 800 degrees per second) that brings the point of maximal visual acuity — the fovea — to the image of interest.

DIENCEPHALIC LOCOMOTOR REGION

Area corresponding to ventral thalamus, which contains neurons that project to reticulospinal neurons, and that thereby can activate the spinal locomotor networks.

MESOPONTINE LOCOMOTOR REGION

Area located at the border between mesencephalon and pons (mesopontine), which contains neurons that project to reticulospinal neurons, and thereby can activate the spinal locomotor networks. This area is often referred to as the mesencephalic locomotor region.

VENTRAL THALAMUS

Nucleus in diencephalon that sends axonal glutamatergic projections to reticulospinal neurons, thereby eliciting locomotor activity. Ventral thalamus should not be confused with the dorsal thalamus, which projects to pallium (corresponding to cortex) as in mammals.

SPIKE-FREQUENCY ADAPTATION

A decrease in the rate of action potentials fired by a neuron under prolonged depolarization.

LEAK CURRENT

Ionic current produced by ion channels that are open at resting membrane potential. They are usually voltage insensitive and often permeable to K+.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Grillner, S. The motor infrastructure: from ion channels to neuronal networks. Nat Rev Neurosci 4, 573–586 (2003). https://doi.org/10.1038/nrn1137

Download citation

Further reading