1932

Abstract

The spinal cord is home to the intrinsic networks for locomotion. An animal in which the spinal cord has been fully severed from the brain can still produce rhythmic, patterned locomotor movements as long as some excitatory drive is provided, such as physical, pharmacological, or electrical stimuli. Yet it remains a challenge to define the underlying circuitry that produces these movements because the spinal cord contains a wide variety of neuron classes whose patterns of interconnectivity are still poorly understood. Computational models of locomotion accordingly rely on untested assumptions about spinal neuron network element identity and connectivity. In this review, we consider the classes of spinal neurons, their interconnectivity, and the significance of their circuit connections along the long axis of the spinal cord. We suggest several lines of analysis to move toward a definitive understanding of the spinal network.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-083122-025325
2023-07-10
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/neuro/46/1/annurev-neuro-083122-025325.html?itemId=/content/journals/10.1146/annurev-neuro-083122-025325&mimeType=html&fmt=ahah

Literature Cited

  1. Abbott LF, Regehr WG. 2004. Synaptic computation. Nature 431:796–803
    [Google Scholar]
  2. Al-Mosawie A, Wilson JM, Brownstone RM. 2007. Heterogeneity of V2-derived interneurons in the adult mouse spinal cord. Eur. J. Neurosci. 26:3003–15
    [Google Scholar]
  3. Alexander T, Nolte C, Krumlauf R. 2009. Hox genes and segmentation of the hindbrain and axial skeleton. Annu. Rev. Cell Dev. Biol. 25:431–56
    [Google Scholar]
  4. Alstermark B, Lundberg A, Pinter M, Sasaki S. 1987. Subpopulations and functions of long C3-C5 propriospinal neurones. Brain Res. 404:395–400
    [Google Scholar]
  5. Alvarez FJ, Fyffe RE. 2007. The continuing case for the Renshaw cell. J. Physiol. 584:31–45
    [Google Scholar]
  6. Alvarez FJ, Jonas PC, Sapir T, Hartley R, Berrocal MC et al. 2005. Postnatal phenotype and localization of spinal cord V1 derived interneurons. J. Comp. Neurol. 493:177–92
    [Google Scholar]
  7. Ampatzis K, Song J, Ausborn J, El Manira A 2014. Separate microcircuit modules of distinct V2a interneurons and motoneurons control the speed of locomotion. Neuron 83:934–43
    [Google Scholar]
  8. Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D et al. 2012. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature 488:642–46
    [Google Scholar]
  9. Ascoli GA, Group PN. 2008. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 9:557–68
    [Google Scholar]
  10. Baek M, Menon V, Jessell TM, Hantman AW, Dasen JS. 2019. Molecular logic of spinocerebellar tract neuron diversity and connectivity. Cell Rep. 27:2620–35.e4
    [Google Scholar]
  11. Bagnall MW, McLean DL. 2014. Modular organization of axial microcircuits in zebrafish. Science 343:197–200
    [Google Scholar]
  12. Baldissera F, Cavallari P, Fournier E, Pierrot-Deseilligny E, Shindo M. 1987. Evidence for mutual inhibition of opposite Ia interneurons in the human upper limb. Exp. Brain Res. 66:106–14
    [Google Scholar]
  13. Bellardita C, Kiehn O. 2015. Phenotypic characterization of speed-associated gait changes in mice reveals modular organization of locomotor networks. Curr. Biol. 25:1426–36
    [Google Scholar]
  14. Berg RW, Alaburda A, Hounsgaard J. 2007. Balanced inhibition and excitation drive spike activity in spinal half-centers. Science 315:390–93
    [Google Scholar]
  15. Berkowitz A. 2002. Both shared and specialized spinal circuitry for scratching and swimming in turtles. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 188:225–34
    [Google Scholar]
  16. Berkowitz A. 2008. Physiology and morphology of shared and specialized spinal interneurons for locomotion and scratching. J. Neurophysiol. 99:2887–901
    [Google Scholar]
  17. Berkowitz A, Roberts A, Soffe SR. 2010. Roles for multifunctional and specialized spinal interneurons during motor pattern generation in tadpoles, zebrafish larvae, and turtles. Front. Behav. Neurosci. 4:36
    [Google Scholar]
  18. Berkowitz A, Stein PS. 1994. Activity of descending propriospinal axons in the turtle hindlimb enlargement during two forms of fictive scratching: phase analyses. J. Neurosci. 14:5105–19
    [Google Scholar]
  19. Bhumbra GS, Bannatyne BA, Watanabe M, Todd AJ, Maxwell DJ, Beato M. 2014. The recurrent case for the Renshaw cell. J. Neurosci. 34:12919–32
    [Google Scholar]
  20. Bhumbra GS, Beato M. 2018. Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic. PLOS Biol. 16:e2003586
    [Google Scholar]
  21. Bikoff JB, Gabitto MI, Rivard AF, Drobac E, Machado TA et al. 2016. Spinal inhibitory interneuron diversity delineates variant motor microcircuits. Cell 165:207–19
    [Google Scholar]
  22. Birinyi A, Viszokay K, Wéber I, Kiehn O, Antal M. 2003. Synaptic targets of commissural interneurons in the lumbar spinal cord of neonatal rats. J. Comp. Neurol. 461:429–40
    [Google Scholar]
  23. Björnfors ER, El Manira A 2016. Functional diversity of excitatory commissural interneurons in adult zebrafish. eLife 5:e18579
    [Google Scholar]
  24. Blacklaws J, Deska-Gauthier D, Jones CT, Petracca YL, Liu M et al. 2015. Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord. Dev. Neurobiol. 75:1003–17
    [Google Scholar]
  25. Böhm UL, Kimura Y, Kawashima T, Ahrens MB, Higashijima S-i et al. 2022. Voltage imaging identifies spinal circuits that modulate locomotor adaptation in zebrafish. Neuron 110:1211–22.e4
    [Google Scholar]
  26. Bonnot A, Whelan PJ, Mentis GZ, O'Donovan MJ. 2002. Locomotor-like activity generated by the neonatal mouse spinal cord. Brain Res. Rev. 40:141–51
    [Google Scholar]
  27. Borowska J, Jones CT, Deska-Gauthier D, Zhang Y. 2015. V3 interneuron subpopulations in the mouse spinal cord undergo distinctive postnatal maturation processes. Neuroscience 295:221–28
    [Google Scholar]
  28. Borowska J, Jones CT, Zhang H, Blacklaws J, Goulding M, Zhang Y. 2013. Functional subpopulations of V3 interneurons in the mature mouse spinal cord. J. Neurosci. 33:18553–65
    [Google Scholar]
  29. Britz O, Zhang J, Grossmann KS, Dyck J, Kim JC et al. 2015. A genetically defined asymmetry underlies the inhibitory control of flexor-extensor locomotor movements. eLife 4:e04718
    [Google Scholar]
  30. Buchanan JT. 2001. Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology. Prog. Neurobiol. 63:441–66
    [Google Scholar]
  31. Butt SJB, Kiehn O. 2003. Functional identification of interneurons responsible for left-right coordination of hindlimbs in mammals. Neuron 38:953–63
    [Google Scholar]
  32. Callahan RA, Roberts R, Sengupta M, Kimura Y, Higashijima SI, Bagnall MW 2019. Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control. eLife 8:e47837
    [Google Scholar]
  33. Callaway EM, Luo L. 2015. Monosynaptic circuit tracing with glycoprotein-deleted rabies viruses. J. Neurosci. 35:8979–85
    [Google Scholar]
  34. Cangiano L. 2005. Mechanisms of rhythm generation in a spinal locomotor network deprived of crossed connections: the lamprey hemicord. J. Neurosci. 25:923–35
    [Google Scholar]
  35. Catela C, Shin MM, Dasen JS. 2015. Assembly and function of spinal circuits for motor control. Annu. Rev. Cell Dev. Biol. 31:669–98
    [Google Scholar]
  36. Cazalets JR, Borde M, Clarac F. 1995. Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat. J. Neurosci. 15:4943–51
    [Google Scholar]
  37. Chalif JI, Martínez-Silva MdL, Pagiazitis JG, Murray AJ, Mentis GZ. 2022. Control of mammalian locomotion by ventral spinocerebellar tract neurons. Cell 185:328–44.e26
    [Google Scholar]
  38. Chevallier S, Jan Ijspeert A, Ryczko D, Nagy F, Cabelguen J-M 2008. Organisation of the spinal central pattern generators for locomotion in the salamander: biology and modelling. Brain Res. Rev. 57:147–61
    [Google Scholar]
  39. Chopek JW, Nascimento F, Beato M, Brownstone RM, Zhang Y. 2018. Sub-populations of spinal V3 interneurons form focal modules of layered pre-motor microcircuits. Cell Rep. 25:146–56.e3
    [Google Scholar]
  40. Cregg JM, Leiras R, Montalant A, Wanken P, Wickersham IR, Kiehn O. 2020. Brainstem neurons that command mammalian locomotor asymmetries. Nat. Neurosci. 23:730–40
    [Google Scholar]
  41. Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE et al. 2008. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron 60:70–83
    [Google Scholar]
  42. Dale N. 2003. Coordinated motor activity in simulated spinal networks emerges from simple biologically plausible rules of connectivity. J. Comput. Neurosci. 14:55–70
    [Google Scholar]
  43. Dale N, Roberts A. 1985. Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos. J. Physiol. 363:35–59
    [Google Scholar]
  44. Danner SM, Shevtsova NA, Frigon A, Rybak IA 2017. Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds. eLife 6:e31050
    [Google Scholar]
  45. Deliagina T, Orlovsky G, Pavlova GA. 1983. The capacity for generation of rhythmic oscillations is distributed in the lumbosacral spinal cord of the cat. Exp. Brain Res. 53:81–90
    [Google Scholar]
  46. Delile J, Rayon T, Melchionda M, Edwards A, Briscoe J, Sagner A 2019. Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord. Development 146:dev173807
    [Google Scholar]
  47. Deska-Gauthier D, Borowska-Fielding J, Jones C, Zhang Y. 2020. The temporal neurogenesis patterning of spinal p3-V3 interneurons into divergent subpopulation assemblies. J. Neurosci. 40:1440–52
    [Google Scholar]
  48. Dougherty KJ, Kiehn O. 2010. Functional organization of V2a-related locomotor circuits in the rodent spinal cord. Ann. N. Y. Acad. Sci. 1198:85–93
    [Google Scholar]
  49. Dougherty KJ, Zagoraiou L, Satoh D, Rozani I, Doobar S et al. 2013. Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons. Neuron 80:920–33
    [Google Scholar]
  50. Eccles JC, Fatt P, Koketsu K. 1954. Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J. Physiol. 126:524–62
    [Google Scholar]
  51. Eccles JC, Fatt P, Landgren S. 1956. Central pathway for direct inhibitory action of impulses in largest afferent nerve fibres to muscle. J. Neurophysiol. 19:75–98
    [Google Scholar]
  52. Fan LZ, Kheifets S, Böhm UL, Wu H, Piatkevich KD et al. 2020. All-optical electrophysiology reveals the role of lateral inhibition in sensory processing in cortical layer 1. Cell 180:521–35.e18
    [Google Scholar]
  53. Fidelin K, Djenoune L, Stokes C, Prendergast A, Gomez J et al. 2015. State-dependent modulation of locomotion by GABAergic spinal sensory neurons. Curr. Biol. 25:3035–47
    [Google Scholar]
  54. Flynn JR, Conn VL, Boyle KA, Hughes DI, Watanabe M et al. 2017. Anatomical and molecular properties of long descending propriospinal neurons in mice. Front. Neuroanat. 11:5
    [Google Scholar]
  55. Francius C, Harris A, Rucchin V, Hendricks TJ, Stam FJ et al. 2013. Identification of multiple subsets of ventral interneurons and differential distribution along the rostrocaudal axis of the developing spinal cord. PLOS ONE 8:e70325
    [Google Scholar]
  56. Gerber V, Yang L, Takamiya M, Ribes V, Gourain V et al. 2019. The HMG box transcription factors Sox1a and b specify a new class of glycinergic interneurons in the spinal cord of zebrafish embryos. Development 146:dev172510
    [Google Scholar]
  57. Gerstmann K, Jurčić N, Blasco E, Kunz S, de Almeida Sassi F et al. 2022. The role of intraspinal sensory neurons in the control of quadrupedal locomotion. Curr. Biol. 32:2442–53.e4
    [Google Scholar]
  58. Gosgnach S, Lanuza GM, Butt SJ, Saueressig H, Zhang Y et al. 2006. V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature 440:215–19
    [Google Scholar]
  59. Goulding M. 2009. Circuits controlling vertebrate locomotion: moving in a new direction. Nat. Rev. Neurosci. 10:507–18
    [Google Scholar]
  60. Griener A, Zhang W, Kao H, Haque F, Gosgnach S. 2017. Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord. Neuroscience 362:47–59
    [Google Scholar]
  61. Griener A, Zhang W, Kao H, Wagner C, Gosgnach S. 2015. Probing diversity within subpopulations of locomotor-related V0 interneurons. Dev. Neurobiol. 75:1189–203
    [Google Scholar]
  62. Grillner S. 1985. Neurobiological bases of rhythmic motor acts in vertebrates. Science 228:143–49
    [Google Scholar]
  63. Grillner S. 2003. The motor infrastructure: from ion channels to neuronal networks. Nat. Rev. Neurosci. 4:573–86
    [Google Scholar]
  64. Grillner S, Jessell TM. 2009. Measured motion: searching for simplicity in spinal locomotor networks. Curr. Opin. Neurobiol. 19:572–86
    [Google Scholar]
  65. Grillner S, Kozlov A, Dario P, Stefanini C, Menciassi A et al. 2007. Modeling a vertebrate motor system: pattern generation, steering and control of body orientation. Prog. Brain Res. 165:221–34
    [Google Scholar]
  66. Guan NN, Xu L, Zhang T, Huang C-X, Wang Z et al. 2021. A specialized spinal circuit for command amplification and directionality during escape behavior. PNAS 118:e2106785118
    [Google Scholar]
  67. Ha NT, Dougherty KJ 2018. Spinal Shox2 interneuron interconnectivity related to function and development. eLife 7:e42519
    [Google Scholar]
  68. Hagglund M, Dougherty KJ, Borgius L, Itohara S, Iwasato T, Kiehn O. 2013. Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion. PNAS 110:11589–94
    [Google Scholar]
  69. Haque F, Gosgnach S. 2019. Mapping connectivity amongst interneuronal components of the locomotor CPG. Front. Cell. Neurosci. 13:443
    [Google Scholar]
  70. Haque F, Rancic V, Zhang W, Clugston R, Ballanyi K, Gosgnach S. 2018. WT1-expressing interneurons regulate left-right alternation during mammalian locomotor activity. J. Neurosci. 38:5666–76
    [Google Scholar]
  71. Häring M, Zeisel A, Hochgerner H, Rinwa P, Jakobsson JET et al. 2018. Neuronal atlas of the dorsal horn defines its architecture and links sensory input to transcriptional cell types. Nat. Neurosci. 21:869–80
    [Google Scholar]
  72. Hayashi M, Hinckley CA, Driscoll SP, Moore NJ, Levine AJ et al. 2018. Graded arrays of spinal and supraspinal V2a interneuron subtypes underlie forelimb and hindlimb motor control. Neuron 97:869–84.e5
    [Google Scholar]
  73. Heckman CJ, Enoka RM. 2012. Motor unit. Compr. Physiol. 2:2629–82
    [Google Scholar]
  74. Higashijima S, Masino MA, Mandel G, Fetcho JR. 2004. Engrailed-1 expression marks a primitive class of inhibitory spinal interneuron. J. Neurosci. 24:5827–39
    [Google Scholar]
  75. Hubbard JM, Bohm UL, Prendergast A, Tseng PB, Newman M et al. 2016. Intraspinal sensory neurons provide powerful inhibition to motor circuits ensuring postural control during locomotion. Curr. Biol. 26:2841–53
    [Google Scholar]
  76. Iglesias González AB, Jakobsson JET, Vieillard J, Lagerström MC, Kullander K, Boije H. 2021. Single cell transcriptomic analysis of spinal Dmrt3 neurons in zebrafish and mouse identifies distinct subtypes and reveal novel subpopulations within the dI6 domain. Front. Cell. Neurosci. 15:781197
    [Google Scholar]
  77. Isaacson JS, Scanziani M. 2011. How inhibition shapes cortical activity. Neuron 72:231–43
    [Google Scholar]
  78. Jankowska E. 1992. Interneuronal relay in spinal pathways from proprioceptors. Prog. Neurobiol. 38:335–78
    [Google Scholar]
  79. Jankowska E. 2001. Spinal interneuronal systems: identification, multifunctional character and reconfigurations in mammals. J. Physiol. 533:31–40
    [Google Scholar]
  80. Jankowska E. 2008. Spinal interneuronal networks in the cat: elementary components. Brain Res. Rev. 57:46–55
    [Google Scholar]
  81. Jankowska E, Smith DO. 1973. Antidromic activation of Renshaw cells and their axonal projections. Acta Physiol. Scand. 88:198–214
    [Google Scholar]
  82. Jha U, Thirumalai V. 2020. Neuromodulatory selection of motor neuron recruitment patterns in a visuomotor behavior increases speed. Curr. Biol. 30:788–801.e3
    [Google Scholar]
  83. Jung H, Baek M, D'Elia KP, Boisvert C, Currie PD et al. 2018. The ancient origins of neural substrates for land walking. Cell 172:667–82.e15
    [Google Scholar]
  84. Juvin L, Le Gal JP, Simmers J, Morin D 2012. Cervicolumbar coordination in mammalian quadrupedal locomotion: role of spinal thoracic circuitry and limb sensory inputs. J. Neurosci. 32:953–65
    [Google Scholar]
  85. Juvin L, Simmers J, Morin D. 2005. Propriospinal circuitry underlying interlimb coordination in mammalian quadrupedal locomotion. J. Neurosci. 25:6025–35
    [Google Scholar]
  86. Kernell D, Verhey BA, Eerbeek O. 1985. Neuronal and muscle unit properties at different rostro-caudal levels of cat's motoneurone pool. Brain Res. 335:71–79
    [Google Scholar]
  87. Kiehn O. 2016. Decoding the organization of spinal circuits that control locomotion. Nat. Rev. Neurosci. 17:224–38
    [Google Scholar]
  88. Kimura Y, Higashijima SI. 2019. Regulation of locomotor speed and selection of active sets of neurons by V1 neurons. Nat. Commun. 10:2268
    [Google Scholar]
  89. Kimura Y, Okamura Y, Higashijima S. 2006. alx, a zebrafish homolog of Chx10, marks ipsilateral descending excitatory interneurons that participate in the regulation of spinal locomotor circuits. J. Neurosci. 26:5684–97
    [Google Scholar]
  90. Kishore S, Bagnall MW, McLean DL. 2014. Systematic shifts in the balance of excitation and inhibition coordinate the activity of axial motor pools at different speeds of locomotion. J. Neurosci. 34:14046–54
    [Google Scholar]
  91. Kishore S, Cadoff EB, Agha MA, McLean DL. 2020. Orderly compartmental mapping of premotor inhibition in the developing zebrafish spinal cord. Science 370:431–36
    [Google Scholar]
  92. Kjaerulff O, Kiehn O. 1996. Distribution of networks generating and coordinating locomotor activity in the neonatal rat spinal cord in vitro: a lesion study. J. Neurosci. 16:5777–94
    [Google Scholar]
  93. Kjaerulff O, Kiehn O. 1997. Crossed rhythmic synaptic input to motoneurons during selective activation of the contralateral spinal locomotor network. J. Neurosci. 17:9433–47
    [Google Scholar]
  94. Knogler LD, Drapeau P. 2014. Sensory gating of an embryonic zebrafish interneuron during spontaneous motor behaviors. Front. Neural Circuits 8:121
    [Google Scholar]
  95. Kohler M, Bengtsson F, Stratmann P, Röhrbein F, Knoll A et al. 2022. Diversified physiological sensory input connectivity questions the existence of distinct classes of spinal interneurons. iScience 25:104083
    [Google Scholar]
  96. Kostyuk PG, Vasilenko DA. 1979. Spinal interneurons. Annu. Rev. Physiol. 41:115–26
    [Google Scholar]
  97. Kozlov A, Huss M, Lansner A, Kotaleski JH, Grillner S. 2009. Simple cellular and network control principles govern complex patterns of motor behavior. PNAS 106:20027–32
    [Google Scholar]
  98. Krumlauf R. 1994. Hox genes in vertebrate development. Cell 78:191–201
    [Google Scholar]
  99. Laliberte AM, Goltash S, Lalonde NR, Bui TV. 2019. Propriospinal neurons: essential elements of locomotor control in the intact and possibly the injured spinal cord. Front. Cell. Neurosci. 13:512
    [Google Scholar]
  100. Lanuza GM, Gosgnach S, Pierani A, Jessell TM, Goulding M. 2004. Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements. Neuron 42:375–86
    [Google Scholar]
  101. Levine AJ, Hinckley CA, Hilde KL, Driscoll SP, Poon TH et al. 2014. Identification of a cellular node for motor control pathways. Nat. Neurosci. 17:586–93
    [Google Scholar]
  102. Li WC, Higashijima S, Parry DM, Roberts A, Soffe SR. 2004. Primitive roles for inhibitory interneurons in developing frog spinal cord. J. Neurosci. 24:5840–48
    [Google Scholar]
  103. Li WC, Roberts A, Soffe SR. 2009. Locomotor rhythm maintenance: electrical coupling among premotor excitatory interneurons in the brainstem and spinal cord of young Xenopus tadpoles. J. Physiol. 587:1677–93
    [Google Scholar]
  104. Liao JC, Fetcho JR. 2008. Shared versus specialized glycinergic spinal interneurons in axial motor circuits of larval zebrafish. J. Neurosci. 28:12982–92
    [Google Scholar]
  105. Lindén H, Petersen PC, Vestergaard M, Berg RW. 2022. Movement is governed by rotational neural dynamics in spinal motor networks. Nature 610:526–31
    [Google Scholar]
  106. Liu Z, Hildebrand DGC, Morgan JL, Jia Y, Slimmon N, Bagnall MW. 2022. Organization of the gravity-sensing system in zebrafish. Nat. Commun. 13:5060
    [Google Scholar]
  107. Ljunggren EE, Haupt S, Ausborn J, Ampatzis K, El Manira A 2014. Optogenetic activation of excitatory premotor interneurons is sufficient to generate coordinated locomotor activity in larval zebrafish. J. Neurosci. 34:134–39
    [Google Scholar]
  108. Marder E, Bucher D. 2001. Central pattern generators and the control of rhythmic movements. Curr. Biol. 11:R986–96
    [Google Scholar]
  109. Marvin JS, Scholl B, Wilson DE, Podgorski K, Kazemipour A et al. 2018. Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR. Nat. Methods 15:936–39
    [Google Scholar]
  110. Marvin JS, Shimoda Y, Magloire V, Leite M, Kawashima T et al. 2019. A genetically encoded fluorescent sensor for in vivo imaging of GABA. Nat. Methods 16:763–70
    [Google Scholar]
  111. McCrea DA, Rybak IA. 2008. Organization of mammalian locomotor rhythm and pattern generation. Brain Res. Rev. 57:134–46
    [Google Scholar]
  112. McLean DL, Dougherty KJ. 2015. Peeling back the layers of locomotor control in the spinal cord. Curr. Opin. Neurobiol. 33:63–70
    [Google Scholar]
  113. McLean DL, Fetcho JR. 2009. Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones. J. Neurosci. 29:13566–77
    [Google Scholar]
  114. McLean DL, Masino MA, Koh IY, Lindquist WB, Fetcho JR. 2008. Continuous shifts in the active set of spinal interneurons during changes in locomotor speed. Nat. Neurosci. 11:1419–29
    [Google Scholar]
  115. Menelaou E, McLean DL. 2019. Hierarchical control of locomotion by distinct types of spinal V2a interneurons in zebrafish. Nat. Commun. 10:4197
    [Google Scholar]
  116. Menelaou E, VanDunk C, McLean DL. 2014. Differences in the morphology of spinal V2a neurons reflect their recruitment order during swimming in larval zebrafish. J. Comp. Neurol. 522:1232–48
    [Google Scholar]
  117. Mentis GZ, Alvarez FJ, Bonnot A, Richards DS, Gonzalez-Forero D et al. 2005. Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. PNAS 102:7344–49
    [Google Scholar]
  118. Moore NJ, Bhumbra GS, Foster JD, Beato M. 2015. Synaptic connectivity between Renshaw cells and motoneurons in the recurrent inhibitory circuit of the spinal cord. J. Neurosci. 35:13673–86
    [Google Scholar]
  119. Ni Y, Nawabi H, Liu X, Yang L, Miyamichi K et al. 2014. Characterization of long descending premotor propriospinal neurons in the spinal cord. J. Neurosci. 34:9404–17
    [Google Scholar]
  120. Nishimaru H, Restrepo CE, Ryge J, Yanagawa Y, Kiehn O. 2005. Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. PNAS 102:5245–49
    [Google Scholar]
  121. Osseward PJ II, Amin ND, Moore JD, Temple BA, Barriga BK et al. 2021. Conserved genetic signatures parcellate cardinal spinal neuron classes into local and projection subsets. Science 372:385–93
    [Google Scholar]
  122. Panayi H, Panayiotou E, Orford M, Genethliou N, Mean R et al. 2010. Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord. J. Neurosci. 30:12274–80
    [Google Scholar]
  123. Perrins R, Soffe SR. 1996. Local effects of glycinergic inhibition in the spinal cord motor systems for swimming in amphibian embryos. J. Neurophysiol. 76:1025–35
    [Google Scholar]
  124. Perry S, Larhammar M, Vieillard J, Nagaraja C, Hilscher MM et al. 2019. Characterization of Dmrt3-derived neurons suggest a role within locomotor circuits. J. Neurosci. 39:1771–82
    [Google Scholar]
  125. Picton LD, Björnfors ER, Fontanel P, Pallucchi I, Bertuzzi M, El Manira A 2022. Developmental switch in the function of inhibitory commissural V0d interneurons in zebrafish. Curr. Biol. 32:3515–28
    [Google Scholar]
  126. Pocratsky AM, Shepard CT, Morehouse JR, Burke DA, Riegler AS et al. 2020. Long ascending propriospinal neurons provide flexible, context-specific control of interlimb coordination. eLife 9:e53565
    [Google Scholar]
  127. Pratt CA, Jordan LM. 1987. Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion. J. Neurophysiol. 57:56–71
    [Google Scholar]
  128. Pujala A, Koyama M 2019. Chronology-based architecture of descending circuits that underlie the development of locomotor repertoire after birth. eLife 8:e42135
    [Google Scholar]
  129. Quinlan KA, Kiehn O. 2007. Segmental, synaptic actions of commissural interneurons in the mouse spinal cord. J. Neurosci. 27:6521–30
    [Google Scholar]
  130. Rancic V, Ballanyi K, Gosgnach S. 2020. Mapping the dynamic recruitment of spinal neurons during fictive locomotion. J. Neurosci. 40:9692–700
    [Google Scholar]
  131. Rancic V, Gosgnach S. 2021. Recent insights into the rhythmogenic core of the locomotor CPG. Int. J. Mol. Sci. 22:1394
    [Google Scholar]
  132. Ronzano R, Bhumbra GS, Brownstone RM, Beato M 2021. Proximal and distal spinal neurons innervating multiple synergist and antagonist motor pools. eLife 10:e70858
    [Google Scholar]
  133. Rosenberg AB, Roco CM, Muscat RA, Kuchina A, Sample P et al. 2018. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science 360:176–82
    [Google Scholar]
  134. Roussel Y, Gaudreau SF, Kacer ER, Sengupta M, Bui TV 2021. Modeling spinal locomotor circuits for movements in developing zebrafish. eLife 10:e67453
    [Google Scholar]
  135. Ruder L, Takeoka A, Arber S. 2016. Long-distance descending spinal neurons ensure quadrupedal locomotor stability. Neuron 92:1063–78
    [Google Scholar]
  136. Russ DE, Cross RBP, Li L, Koch SC, Matson KJE et al. 2021. A harmonized atlas of mouse spinal cord cell types and their spatial organization. Nat. Commun. 12:5722
    [Google Scholar]
  137. Sathyamurthy A, Johnson KR, Matson KJE, Dobrott CI, Li L et al. 2018. Massively parallel single nucleus transcriptional profiling defines spinal cord neurons and their activity during behavior. Cell Rep. 22:2216–25
    [Google Scholar]
  138. Satou C, Kimura Y, Higashijima S. 2012. Generation of multiple classes of V0 neurons in zebrafish spinal cord: progenitor heterogeneity and temporal control of neuronal diversity. J. Neurosci. 32:1771–83
    [Google Scholar]
  139. Satou C, Kimura Y, Kohashi T, Horikawa K, Takeda H et al. 2009. Functional role of a specialized class of spinal commissural inhibitory neurons during fast escapes in zebrafish. J. Neurosci. 29:6780–93
    [Google Scholar]
  140. Satou C, Sugioka T, Uemura Y, Shimazaki T, Zmarz P et al. 2020. Functional diversity of glycinergic commissural inhibitory neurons in larval zebrafish. Cell Rep. 30:3036–50.e4
    [Google Scholar]
  141. Sengupta M, Bagnall MW. 2022. V2b neurons act via multiple targets in spinal motor networks. bioRxiv 2022.08.01.502410. https://doi.org/10.1101/2022.08.01.502410
  142. Sengupta M, Daliparthi V, Roussel Y, Bui TV, Bagnall MW. 2021. Spinal V1 neurons inhibit motor targets locally and sensory targets distally. Curr. Biol. 31:3820–33
    [Google Scholar]
  143. Shevtsova NA, Rybak IA. 2016. Organization of flexor-extensor interactions in the mammalian spinal cord: insights from computational modelling. J. Physiol. 594:6117–31
    [Google Scholar]
  144. Shevtsova NA, Talpalar AE, Markin SN, Harris-Warrick RM, Kiehn O, Rybak IA. 2015. Organization of left-right coordination of neuronal activity in the mammalian spinal cord: insights from computational modelling. J. Physiol. 593:2403–26
    [Google Scholar]
  145. Siembab VC, Smith CA, Zagoraiou L, Berrocal MC, Mentis GZ, Alvarez FJ. 2010. Target selection of proprioceptive and motor axon synapses on neonatal V1-derived Ia inhibitory interneurons and Renshaw cells. J. Comp. Neurol. 518:4675–701
    [Google Scholar]
  146. Soffe SR, Clarke JD, Roberts A. 1984. Activity of commissural interneurons in spinal cord of Xenopus embryos. J. Neurophysiol. 51:1257–67
    [Google Scholar]
  147. Soffe SR, Zhao F-Y, Roberts A. 2001. Functional projection distances of spinal interneurons mediating reciprocal inhibition during swimming in Xenopus tadpoles. Eur. J. Neurosci. 13:617–27
    [Google Scholar]
  148. Song J, Ampatzis K, Bjornfors ER, El Manira A 2016. Motor neurons control locomotor circuit function retrogradely via gap junctions. Nature 529:399–402
    [Google Scholar]
  149. Song J, Dahlberg E, El Manira A 2018. V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements. Nat. Commun. 9:3370
    [Google Scholar]
  150. Svara FN, Kornfeld J, Denk W, Bollmann JH. 2018. Volume EM reconstruction of spinal cord reveals wiring specificity in speed-related motor circuits. Cell Rep. 23:2942–54
    [Google Scholar]
  151. Sweeney LB, Bikoff JB, Gabitto MI, Brenner-Morton S, Baek M et al. 2018. Origin and segmental diversity of spinal inhibitory interneurons. Neuron 97:341–55.e3
    [Google Scholar]
  152. Talpalar AE, Bouvier J, Borgius L, Fortin G, Pierani A, Kiehn O. 2013. Dual-mode operation of neuronal networks involved in left-right alternation. Nature 500:85–88
    [Google Scholar]
  153. Tunstall MJ, Roberts A. 1994. A longitudinal gradient of synaptic drive in the spinal cord of Xenopus embryos and its role in co-ordination of swimming. J. Physiol. 474:393–405
    [Google Scholar]
  154. Uemura Y, Kato K, Kawakami K, Kimura Y, Oda Y, Higashijima S-I. 2020. Neuronal circuits that control rhythmic pectoral fin movements in zebrafish. J. Neurosci. 40:6678–90
    [Google Scholar]
  155. Usseglio G, Gatier E, Heuzé A, Hérent C, Bouvier J. 2020. Control of orienting movements and locomotion by projection-defined subsets of brainstem V2a neurons. Curr. Biol. 30:4665–81.e6
    [Google Scholar]
  156. Wiggin TD, Anderson TM, Eian J, Peck JH, Masino MA. 2012. Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization. J. Neurophysiol. 108:925–34
    [Google Scholar]
  157. Wiggin TD, Montgomery JE, Brunick AJ, Peck JH, Masino MA. 2022. V3 interneurons are active and recruit spinal motor neurons during in vivo fictive swimming in larval zebrafish. eNeuro 9:ENEURO.0476–21.2022
    [Google Scholar]
  158. Wilson JM, Blagovechtchenski E, Brownstone RM. 2010. Genetically defined inhibitory neurons in the mouse spinal cord dorsal horn: a possible source of rhythmic inhibition of motoneurons during fictive locomotion. J. Neurosci. 30:1137–48
    [Google Scholar]
  159. Wolf E, Soffe SR, Roberts A. 2009. Longitudinal neuronal organization and coordination in a simple vertebrate: a continuous, semi-quantitative computer model of the central pattern generator for swimming in young frog tadpoles. J. Comput. Neurosci. 27:291–308
    [Google Scholar]
  160. Wu M-Y, Carbo-Tano M, Mirat O, Lejeune F-X, Roussel J et al. 2021. Spinal sensory neurons project onto the hindbrain to stabilize posture and enhance locomotor speed. Curr. Biol. 31:3315–29.e5
    [Google Scholar]
  161. Zagoraiou L, Akay T, Martin JF, Brownstone RM, Jessell TM, Miles GB. 2009. A cluster of cholinergic premotor interneurons modulates mouse locomotor activity. Neuron 64:645–62
    [Google Scholar]
  162. Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F et al. 2018. Molecular architecture of the mouse nervous system. Cell 174:999–1014.e22
    [Google Scholar]
  163. Zhang H, Shevtsova NA, Deska-Gauthier D, Mackay C, Dougherty KJ et al. 2022. The role of V3 neurons in speed-dependent interlimb coordination during locomotion in mice. eLife 11:e73424
    [Google Scholar]
  164. Zhang J, Lanuza GM, Britz O, Wang Z, Siembab VC et al. 2014. V1 and V2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion. Neuron 82:138–50
    [Google Scholar]
  165. Zhang Y, Narayan S, Geiman E, Lanuza GM, Velasquez T et al. 2008. V3 spinal neurons establish a robust and balanced locomotor rhythm during walking. Neuron 60:84–96
    [Google Scholar]
  166. Zhong G, Droho S, Crone SA, Dietz S, Kwan AC et al. 2010. Electrophysiological characterization of V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J. Neurosci. 30:170–82
    [Google Scholar]
  167. Zhong G, Sharma K, Harris-Warrick RM. 2011. Frequency-dependent recruitment of V2a interneurons during fictive locomotion in the mouse spinal cord. Nat. Commun. 2:274
    [Google Scholar]
/content/journals/10.1146/annurev-neuro-083122-025325
Loading
/content/journals/10.1146/annurev-neuro-083122-025325
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error