Key Points
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The central pattern generator (CPG) networks that generate relatively simple motor outputs are ideal experimental models for circuit analysis.
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Locomotor CPGs in the ventral spinal cord function autonomously to generate repetitive patterns of oscillatory motor activity.
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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.
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The development and assembly of the locomotor CPG is regulated by a genetic programme that operates in the embryonic spinal cord.
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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.
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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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References
Dickinson, M. H. et al. How animals move: an integrative view. Science 288, 100â106 (2000).
Grillner, S. Locomotion in vertebrates: central mechanisms and reflex interactions. Physiol. Rev. 55, 247â304 (1975).
Orlovsky, G. N., Deliagina, T. G. & Grillner, S. Neural Control of Locomotion. From mollusc to man (Oxford Univ. Press, New York, 1999). This text provides a good introduction and overview of the neural control of locomotion.
Marder, E. & Bucher, D. Central pattern generators and the control of rhythmic movements. Curr. Biol. 11, R986âR996 (2001). This is an outstanding review that outlines many of the basic principles that operate in rhythmic motor systems. It draws on the invertebrate and vertebrate literature to give an integrative overview of how CPGs are organized and operate.
Grillner, S. The motor infrastructure: from ion channels to neuronal networks. Nature Rev. Neurosci. 4, 573â586 (2003). This excellent review focuses primarily on the lamprey and outlines the crucial findings and principles that underlie the rhythmic motor patterns that control swimming movements. It provides a detailed overview of the swimming CPG.
Grillner, S. Biological pattern generation: the cellular and computational logic of networks in motion. Neuron 52, 751â766 (2007). An important review that outlines many of the basic features of locomotor networks.
Roberts, A., Soffe, S. R., Wolf, E. S., Yoshida, M. & Zhao, F. Y. Central circuits controlling locomotion in young frog tadpoles. Ann. NY Acad. Sci. 860, 19â34 (1998).
Dale, N. & Kuenzi, F. M. Ion channels and the control of swimming in the Xenopus embryo. Prog. Neurobiol. 35, 729â756 (1997).
Nguyen, Q. T. & Kleinfeld, D. Positive feedback in a brainstem tactile sensorimotor loop. Neuron 45, 447â457 (2005).
Lund, J. P. & Kolta, A. Generation of the central masticatory pattern and its modification by sensory feedback. Dysphagia 21, 167â174 (2006).
Ramirez, J.-M. & Richter, D. W. The neuronal mechanisms of respiratory rhythm generation. Curr. Opin. Neurobiol. 6, 817â825 (1996).
Feldman, J. L. & Del-Negro, C. A. Looking for inspiration: new perspectives on respiratory rhythm. Nature Rev. Neurosci. 7, 232â242 (2006).
Kiehn, O. Locomotor circuits in the mammalian spinal cord. Ann. Rev. Neurosci. 29, 279â306 (2006).
Sherrington, C. S. The Integrative Action of the Nervous System (Yale Univ. Press, New Haven, 1906).
Eccles, J. C. The Physiology of Nerve Cells (Johns Hopkins Univ. Press, Baltimore, 1968).
Lundberg, A. Multisensory control of spinal reflex pathways. Prog. Brain Res. 50, 11â28 (1979).
Jankowska, E. & Edgley, S. Interactions between pathways controlling posture and gait at the level of spinal interneurons. Prog. Brain Res. 97, 161â171 (1993).
Jankowska, E. Spinal interneuronal systems: identification, multifunctional character and reconfigurations in mammals. J. Physiol. 533, 31â40 (2001).
Brown, G. T. On the nature of the fundamental activity of the nervous centres. J. Physiol. 48, 18â46 (1914).
Wilson, D. M. & Wyman, R. J. Motor output patterns during random and rhythmic stimulation of locust thoracic ganglia. Biophys. J. 5, 121â143 (1965).
Grillner, S. & Zangger, P. On the central generation of locomotion in the low spinal cat. Exp. Brain Res. 34, 241â261 (1979).
Armstrong, D. M. Supraspinal contributions to the initiation and control of locomotion in the cat. Prog. Neurobiol. 26, 273â361 (1986).
Jordan, L. M. Initiation of locomotion in mammals. Ann. NY Acad. Sci. 860, 83â93 (1998).
Drew, T., Prentice, S. & Schepens, B. Cortical and brainstem control of locomotion. Prog. Brain Res. 143, 251â261 (2004).
Rossignol, S., Dubuc, R. & Gossard, J.-P. Dynamic sensorimotor interactions in locomotion. Physiol. Rev. 86, 89â154 (2005). An important review that comprehensively covers the role of sensory feedback in locomotion.
Liddell, E. G. T. & Sherrington, C. S. Recruitment and some other factors of reflex inhibition. Proc. R. Soc. Lond. B Biol. Sci. 97, 488â518 (1925).
Burke, R. E. in Motor Control: Concepts and Issues (eds Humphrey, D. R. & Freund, H. J.) 5â21 (John Wiley and Sons, Chichester, 1991).
Henneman, E., Clamann, H. P., Gillies, J. D. & Skinner, R. D. Rank order of motoneurons within a pool: law of combination. J. Neurophysiol. 37, 1338â1349 (1974).
Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Rev. Genet. 1, 20â29 (2000). Many of the key conceptual findings regarding the patterning and specification of spinal cord cell types during embryonic development are outlined in this excellent review. Although the specification of motor neurons is emphasized, the general mechanisms that operate in motor neurons are also likely to regulate interneuron differentiation.
Shirasaki, R. & Pfaff, S. L. Transcriptional codes and the control of neuronal identity. Annu. Rev. Neurosci. 25, 251â281 (2002).
Goulding, M., Lanuza, G., Sapir, T. & Narayan, S. The formation of sensorimotor circuits. Curr. Opin. Neurobiol. 12, 505â515 (2002).
Kullander, K. & Kiehn, O. Central pattern generators deciphered by molecular genetics. Neuron 41, 317â321 (2004).
Goulding, M. & Pfaff, S. L. Development of circuits that generate simple rhythmic behaviors in vertebrates. Curr. Opin. Neurobiol. 15, 14â20 (2005).
Ladle, D. R., Pecho-Vriesling, E. & Arber, S. Assembly of motor circuits in the spinal cord: driven to function by genetic and experience-dependent mechanisms. Neuron 56, 270â283 (2007). A recent review that nicely summarizes our current understanding of how sensorimotor circuits develop.
Yu, C. R. et al. Spontaneous neural activity is required for the establishment and maintainance of the olfactory sensory map. Neuron 42, 553â566 (2004).
Gosgnach, S. et al. V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature 440, 215â219 (2006).
Dymecki, S. M. & Kim, J. C. Molecular neuroanatomy's âthree Gsâ: a primer. Neuron 54, 17â34 (2007). This review describes the increasingly sophisticated methods that can be used to study neural development and manipulate neurons in the mouse. A broad range of techniques are covered, including the use of intersectional approaches that use Cre and Flp recombinases to further refine specificity.
Lerchner, W. et al. Reversible silencing of neuronal excitability in behaving mice by a genetically targeted, ivermectin-gated chloride channel. Neuron 54, 35â49 (2007). This paper, together with references 36,40,99 and 116, describes cutting-edge genetic technologies for regulating neuronal excitability and transmission in mice.
Crone, S. A. et al. Genetic ablation of V2a ipsilateral interneurons disrupts left-right motor coordination in mammalian spinal cord. Neuron 60, 70â83 (2008).
Zhang, Y. et al. V3 spinal neurons establish a robust and balanced motor rhythm during walking. Neuron 60, 84â96 (2008).
Fetcho, J. R. & Bhatt, D. H. Genes and photons: new avenues into the neuronal basis of behavior. Curr. Opin. Neurobiol. 14, 707â714 (2004).
Marder, E. & Calabrese, R. L. Principles of motor pattern generation. Physiol. Rev. 76, 687â717 (1996).
Meyrand, P., Simmers, J. & Moulins, M. Construction of a pattern generating circuit with neurons of different networks. Nature 351, 60â63 (1991).
Weimann, J. M., Meyrand, P. & Marder, E. Neurons that form multiple pattern generators: identification and multiple activity patterns of gastric/pyloric neurons in the crab stomatogastric system. J. Neurophysiol. 65, 111â122 (1991).
Kristan, W. B. Jr, Calabrese, R. L. & Friesen, W. O. Neuronal control of leech behavior. Prog. Neurobiol. 76, 279â327 (2005).
Briggman, K. L., Abarbanel, H. D. & Kristan, W. B. Jr. Optical imaging of neuronal populations during decision making. Science 307, 896â901 (2005).
Berkowitz, A. Physiology and morphology of shared and specialized spinal interneurons for locomotion and scratching. J. Neurophysiol. 99, 2887â2901 (2008).
Hooper, S. L. & Marder, E. Modulation of the pyloric rhythm by the peptide proctolin. J. Neurosci. 7, 2097â2112 (1987).
Harris-Warrick, R. M. & Flamm, R. E. Multiple mechanisms of bursting in a conditional bursting neuron. J. Neurosci. 7, 2113â2128 (1987).
Ramirez, J.-M., Tryba, A. K. & Pena, F. Pacemaker neurons and neuronal networks: an integrative view. Curr. Opin. Neurobiol. 14, 665â674 (2004).
Satterlie, R. A. Reciprocal inhibition and postinhibitory rebound produce reverberation in a locomotor pattern generator. Science 229, 402â404 (1985).
Buchanan, J. T. Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. J. Neurophysiol. 81, 2037â2045 (1999).
Cohen, A. H. & Harris-Warrick, R. M. Strychnine eliminates alternating motor output during fictive locomotion in the lamprey. Brain Res. 293, 164â167 (1984).
Cowley, K. C. & Schmidt, B. J. Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord. J. Neurophysiol. 74, 1109â1117 (1995).
Kudo, N. & Yamada, T. NMDA-induced locomotor activity in a spinal cord-hindlimb muscle preparation of the newborn rat studied in vitro. Neurosci. Lett. 75, 43â48 (1987).
Smith. J. C., Liu, G. & Feldman, J. L. Neural mechanisms generating locomotion studied in mammalian hindbrain-spinal cord in vitro. FASEB J. 2, 2283â2288 (1988).
Cazalets, J. R., Grillner, P., Menard, I., Cremieux, J. & Clarac, F. Two types of motor rhythm generated by NMDA and amines in an in vitro preparation of neonatal rat. Neurosci. Lett. 111, 116â121 (1990).
Sapir, T. et al. Pax6 and En1 regulate two critical aspects of Renshaw cell development. J. Neurosci. 24, 1255â1264 (2004).
Alvarez. F. et al. Postnatal phenotype and localization of V1-derived interneurons. J. Comp. Neurol. 493, 177â192 (2005).
Wang, Z., Li, L., Goulding, M. & Frank, E. Early postnatal development of reciprocal inhibition in the murine spinal cord. J. Neurophysiol. 100, 185â196 (2008).
Cowley, K. C. & Schmidt, B. J. Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. J. Neurophysiol. 77, 247â259 (1997).
Kremer, E. & Lev-Tov, A. Localization of the spinal network associated with the generation of hindlimb locomotion in the neonatal rat and organization of its transverse coupling system. J. Neurophysiol. 77, 1155â1170 (1997).
Kjaerulff, O. & Kiehn, O. Distribution of networks generating and coordinating locomotor activity in the neonatal rat spinal cord in vitro. J. Neurosci. 16, 5777â5794 (1996).
Barajon, I., Gossard, J.-P. & Hultborn, H. Induction of fos expression by activity in the spinal rhythm generator for scratching. Brain Res. 588, 168â172 (1992).
Cina, C. & Hochman, S. Diffuse distribution of sulforhodamine-labeled neurons during serotonin-evoked locomotion in the neonatal rat thoracolumbar spinal cord. J. Comp. Neurol. 423, 590â602 (2000).
Dai, X., Noga, B. R., Douglas, J. R. & Jordan, L. M. Localization of spinal neurons activated during locomotion using the c-fos immunohistochemical method. J. Neurophysiol. 93, 3442â3452 (2005).
Lanuza, G. M., Gosgnach, S., Pierani, A., Jessell, T. M. & Goulding, M. Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements. Neuron 42, 375â386 (2004).
Gross, M. K., Dottori, M. & Goulding, M. Lbx1 specifies somatosensory association neurons in the dorsal spinal cord. Neuron 34, 535â549 (2002).
Muller, T. et al. The homeodomain factor Lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord. Neuron 34, 551â562 (2002).
Lee, K. & Jessell, T. M. The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci. 22, 261â294 (1999).
Peng, C.-Y. et al. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron 53, 813â827 (2007).
Lundfald, L. et al. Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing spinal cord. Eur. J. Neurosci. 26, 2989â3002 (2007).
Al-Mosawie, A., Wilson, J. M. & Brownstone, R. M. Heterogeneity of V2-derived interneurons in the adult mouse spinal cord. Eur. J. Neurosci. 26, 3003â3015 (2007).
Moran-Rivard, L. et al. Evx1 is a postmitotic determinant of V0 interneuron identity in the spinal cord. Neuron 29, 385â399 (2001).
Pierani, A. et al. Control of interneuron fate in the developing spinal cord by the progenitor homeodomain factor Dbx1. Neuron 29, 367â384 (2001).
Saueressig, H., Burrill, J. & Goulding, M. En1 and Netrin-1 control two distinct aspects of axon growth in association interneurons that project to motor neurons. Development 126, 4201â4212 (1999).
Matise, M. P. & Joyner, A. L. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J. Neurosci. 17, 7805â7816 (1997).
Wenner, P., O'Donovan, M. J. & Matise, M. P. Topological and physiological characterization of interneurons that express Engrailed-1 in the embryonic chick spinal cord. J. Neurophysiol. 84, 2651â2657 (2000).
Li, W. C., Higashijima, S., Parry, D. M., Roberts, A. & Soffe, S. R. Primitive roles for inhibitory neurons in developing frog spinal cord. J. Neurosci. 24, 5840â5848 (2004).
Higashijima, S., Masino, M. A., Mandel, G. & Fetcho, J. R. Engrailed-1 expression marks a primitive class of inhibitory spinal interneuron. J. Neurosci. 24, 5827â5839 (2004).
Kato, M. Chronically isolated lumbar spinal cord generates locomotor activities in the ipsilatateral hindlimb of the cat. Neurosci. Res. 9, 22â34 (1990).
Kjaerulff, O. & Kiehn, O. Crossed rhythmic synaptic input to motoneurons during selective activation of the contralateral spinal locomotor network. J. Neurosci. 17, 9433â9447 (1997).
Soffe, S. R., Clarke, J. D. W. & Roberts, A. Activity of commissural interneurones in the spinal cord of Xenopus embryos. J. Neurophysiol. 51, 1257â1267 (1984).
Dale, N., Reciprocal inhibitory interneurons in the Xenopus embryo. J. Physiol. 363, 61â70 (1985).
Dottori, M. et al. EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract. Proc. Natl Acad. Sci. USA 95, 13248â13253 (1998).
Kullander, K. et al. Role of EphA4 and EphrinB3 in local neuronal circuits that control walking. Science 299, 1889â1892 (2003).
Fawcett, J. P. et al. Nck adaptors control the organization of neuronal circuits important for walking. Proc. Natl Acad. Sci. USA 104, 20973â20978 (2007).
Butt, S. J., Lundfald, L. & Kiehn, O. EphA4 defines a class of excitatory locomotor-related interneurons. Proc. Natl Acad. Sci. USA 102, 14098â14103 (2005).
Hirata, H. et al. Zebrafish bandoneon mutants display behavioural defects due to a mutation in the glycine receptor beta subunit. Proc. Natl Acad. Sci. USA 102, 8345â8350 (2005).
Cui, W. W. et al. The zebrafish shocked gene encodes a glycine transporter and is essential for the function of early neural circuits in the CNS. J. Neurosci. 25, 6610â6620 (2005).
Higashijima, S., Mandel, G. & Fetcho, J. Distribution of prospective glutamatergic, glycinergic and GABAergic neurons in the larval zebrafish. J. Comp. Neurol. 480, 1â18 (2004).
Higashijima, S., Schaefer, M. & Fetcho, J. R. Neurotransmitter properties of spinal neurons in embryonic and larval zebrafish. J. Comp. Neurol. 480, 19â37 (2004).
Lorent, K., Liu, K. S., Fetcho, J. R. & Granato, M. The zebrafish space cadet gene controls axonal pathfinding of neurons that modulate fast turning movements. Development 128, 2131â2142 (2001).
Kuranaratne, A., Hargrave, M., Poh, A. & Yamada, T. GATA proteins identify a novel ventral interneuron subclass in the developing chick spinal cord. Dev. Biol. 249, 30â43 (2002).
Wilson, J., M. et al. Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. J. Neurosci. 25, 5710â5719 (2005).
Hinckley, C. A., Hartley, R., Wu, L., Todd, A. & Ziskind-Conhaim, L. Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord. J. Neurophysiol. 93, 1439â1449 (2005).
Hinckley, C. A. & Ziskind-Conhaim, L. Electrical coupling between locomotor-related excitatory neurons in the mammalian spinal cord. J. Neurosci. 16, 8477â8483 (2006).
Brownstone, R. M. & Wilson, J. M. Strategies for delineating spinal locomotor rhythm-generating networks and the possible role of Hb9 interneurones in rhythmogenesis. Brain Res. Rev. 57, 64â76 (2008).
Tan, E. M. et al. Selective and quickly reversible inactivation of mammalian neurons using the Drosophila allatostatin receptor. Neuron 51, 157â170 (2006).
Tan, W. et al. Silencing preBotzinger Complex somatostatin-expressing neurons induces persistent apnea in awake rat. Nature Neurosci. 11, 538â540 (2008).
Pratt, C. A. & Jordan, L. M. Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion. J. Neurophysiol. 57, 56â71 (1987).
Lewis, K. E. & Eisen, J. S. From cells to circuits: development of the zebrafish spinal cord. Prog. Neurobiol. 69, 419â449 (2003).
Kimura, Y., Okamura, Y. & Higashijima, S. alx, a zebrafish homologue of Chx10, marks ipsilateral descending excitatory interneurons that participate in the regulation of spinal locomotor circuits. J. Neurosci. 26, 5684â5697 (2006).
Batista, M. F., Jacobstein, J. & Lewis, K. E. Zebrafish V2 cells develop into excitatory CiD and Notch signaling dependent inhibitory VeLD neurons. Dev. Biol. 322, 263â275 (2008).
Combes, D., Merrywest, S. D., Simmers, J. & Sillar, K. T. Developmental segregation of spinal networks driving axial and hindlimb-based locomotion in metamorphosing Xenopus laevis. J. Physiol. 559, 17â24 (2004).
Neyt, C. et al. Evolutionary origins of vertebrate appendicular muscle. Nature 408, 82â86 (2000).
Gross, M. K. et al. Lbx1 is required for muscle precursor migration along a lateral pathway into the limb. Development 127, 413â424 (1999).
Brohmann, H., Jagla, K. & Birchmeier, C. The role of Lbx1 in the migration of muscle precursor cells. Development 127, 437â445 (2000).
Thorsen, D. H., Cassidy, J. J. & Hale, M. E. Swimming of larval zebrafish: fin-axis coordination and implications for function and neural control. J. Exp. Biol. 207, 4175â4183 (2004).
Ijspeert, A. J., Crespi, A., Ryczko, D. & Cabelguen, J. M. From swimming to walking with a salamander robot driven by a spinal cord model. Science 315, 1352â1353 (2007).
Meisenbock, G. & Kevrekidis, I. G. Optical imaging and control of genetically designated neurons in functioning circuits. Annu. Rev. Neurosci. 28, 533â563 (2005).
Zhang, F., Aravanis, A. M., Adamantidis, A., de Lecea, L. & Deisseroth, K. Circuit breakers: optical technologies for probing neural signals and systems. Nature Rev. Neurosci. 8, 577â581 (2007).
Herlitze, S. & Landmesser, L. T. New optical tools for controlling neuronal activity. Curr. Opin. Neurobiol. 17, 87â94 (2007).
Douglass, A. D., Kraves, S., Deisseroth, K., Schier, A. F. & Engert, F. Escape behavior elicited by single channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons. Curr. Biol. 18, 1133â2237 (2008).
Ambruster, B. N., Li, X., Pausch, M., Herlitze, S. & Roth, B. L. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl Acad. Sci. USA 104, 5163â5168 (2007).
Nakashiba, T., Young, J. Z., McHugh, T. J., Buhl, D. L. & Tonegawa, S. Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319, 1260â1264 (2008).
Gray, P. A. et al. Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 306, 2255â2257 (2004).
Wilson, J., Dombeck, D. A., Diaz-Rios, M., Harris-Warrick, R. M. & Brownstone, R. M. Two-photon calcium imaging of a network activity in XFP-expressing neurons in the mouse. J. Neurophysiol. 97, 3118â3125 (2007).
Bonnot, A., Mentis, G. Z., Skoch, J. & O'Donovan, M. J. Electroporation loading of calcium-sensitive dyes into the CNS. J. Neurophysiol. 93, 1793â1808 (2004).
Hale, M. E., Ritter, D. A. & Fetcho, J. R. A confocal study of spinal interneurons in living larval zebrafish. J. Comp. Neurol. 437, 1â16 (2001).
Bhatt, D. H., McLean, D. L., Hale, M. E. & Fetcho, J. R. Graded movement strength by changes in firing intensity versus recruitment of spinal interneurons. Neuron 53, 91â102 (2007).
McLean, D. L., Fan, J., Higashijima, S., Hale, M. E. & Fetcho, J. R. A topographic map of recruitment in spinal cord. Nature 446, 71â75 (2007).
O'Donovan, M. J. & Landmesser, L. T. The development of hindlimb motor activity studied in the isolated spinal cord of the chick embryo. J. Neurosci. 7, 3256â3264 (1987).
Myers, C. P. et al. Cholinergic input is required during embryonic development to mediate proper assembly of spinal locomotor circuits. Neuron 46, 37â49 (2005).
Jean-Xavier, C., Mentis, G. Z., O'Donovan, M. J., Cattaert, D. & Vinay, L. Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Proc. Natl Acad. Sci. USA 104, 11477â11482 (2007).
Nishimura, H., Iizuka, M., Ozaki, S. & Kudo, N. Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro. J. Physiol. 497, 131â143 (1996).
Borodinsky, L. N. et al. Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429, 523â530 (2004).
Goulding, M. A matter of balance. Nature 429, 515â517 (2004).
Hanson, M.G. & Landmesser, L. T. Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. Neuron 43, 687â701 (2004).
Schouenberg, J. Learning in sensorimotor circuits. Curr. Opin. Neurobiol. 14, 693â697 (2004).
Hounsgaard, J. & Kjaerulff, O. Plateau potentials in a subpopulation of interneurons in the ventral horn of the turtle spinal cord. Eur. J. Neurosci. 4, 183â188 (1992).
Kiehn, O., Johnson, B. R. & Raastad, M. Plateau potentials in mammalian interneurons during transmitter-induced locomotor activity. Neuroscience 75, 263â273 (1996).
Zhang, B. & Harris-Warrick, R. M. Calcium-dependent plateau potentials in a crab stomatogastric ganglion motor neuron. J. Neurophysiol. 74, 1929â1937 (1995).
Buchanan, J. T. & Grillner, S. Newly identified glutamate inteneurons and their role in locomotion in the lamprey spinal cord. Science 236, 312â314 (1987).
Roberts, A. Early functional organization of spinal neurons in developing lower vertebrates. Brain Res. Bull. 53, 585â593 (2000).
Li, W. C., Soffe, S., Wolf, E. & Roberts, A, Persistent responses to brief stimuli: feedback excitation among brainstem neurons. J. Neurosci. 26, 4026â4035 (2006).
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
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Neurons whose axons cross from one side of the spinal cord to the other.
- Ventricular zone
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Innermost layer of the embryonic spinal cord that contains dividing progenitor cells.
- Alar plate
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Dorsal region of the ventricular zone in the embryonic spinal cord.
- Lineage tracing studies
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Techniques that allow the progeny of a cell in the embryo to be traced.
- Fictive locomotion
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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, 507â518 (2009). https://doi.org/10.1038/nrn2608
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DOI: https://doi.org/10.1038/nrn2608
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