Abstract
This chapter reviews recent work showing that vertebrate motoneurons can trigger spontaneous rhythmic activity in the developing spinal cord and can modulate the function of several different central pattern generators later in development. In both the embryonic chick and the fetal mouse spinal cords, antidromic activation of motoneurons can trigger bouts of rhythmic activity. In the neonatal mouse, optogenetic manipulation of motoneuron firing can modulate the frequency of fictive locomotion activated by a drug cocktail. In adult animals, motoneurons have been shown to regulate swimming in the zebrafish, and vocalization in fish and frogs. We discuss the significance of these findings and the degree to which motoneurons may be considered a part of these central pattern generators.
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References
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(4):934–943
Arai Y, Mentis GZ, Wu JY, O’Donovan MJ (2007) Ventrolateral origin of each cycle of rhythmic activity generated by the spinal cord of the chick embryo. PLoS One 2(5):e417
Bass AH, Marchaterre MA, Baker R (1994) Vocal-acoustic pathways in a teleost fish. J Neurosci 14(7):4025–4039
Beattie MS, Bresnahan JC, Mawe GM, Finn S (1987) Distribution and ultrastructure of ventral root afferents to lamina I of the cat sacral spinal cord. Neurosci Lett 76(1):1–6
Bhumbra GS, Beato M (2018) Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic. PLoS Biol 16(3):e2003586
Bonnot A, Chub N, Pujala A, O’Donovan MJ (2009) Excitatory actions of ventral root stimulation during network activity generated by the disinhibited neonatal mouse spinal cord. J Neurophysiol 101(6):2995–3011
Borodinsky LN, Root CM, Cronin JA, Sann SB, Gu X, Spitzer NC (2004) Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429(6991):523–530
Brock LG, Coombs JS, Eccles JC (1952) The recording of potentials from motoneurones with an intracellular electrode. J Physiol 117(4):431–460
Cazalets JR, Sqalli-Houssaini Y, Clarac F (1992) Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat. J Physiol 455:187–204
Chagnaud BP, Baker R, Bass AH (2011) Vocalization frequency and duration are coded in separate hindbrain nuclei. Nat Commun 2(1):346
Chagnaud BP, Bass AH (2014) Vocal behavior and vocal central pattern generator organization diverge among toadfishes. Brain Behav Evol 84(1):51–65
Chagnaud BP, Perelmuter JT, Forlano PM, Bass AH (2021) Gap junction-mediated glycinergic inhibition ensures precise temporal patterning in vocal behavior. elife 10
Chalif JI, Martínez-Silva MDL, Pagiazitis JG, Murray AJ, Mentis GZ (2022) Control of mammalian locomotion by ventral spinocerebellar tract neurons. Cell 185(2):328–344.e326
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(1):146–156 e143
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463(7277):98–102
Chub N, O’Donovan MJ (2001) Post-episode depression of GABAergic transmission in spinal neurons of the chick embryo. J Neurophysiol 85(5):2166–2176
Chung JM, Lee KH, Endo K, Coggeshall RE (1983) Activation of central neurons by ventral root afferents. Science 222(4626):934–935
Chung JM, Lee KH, Kim J, Coggeshall RE (1985) Activation of dorsal horn cells by ventral root stimulation in the cat. J Neurophysiol 54(2):261–272
Clifton GL, Coggeshall RE, Vance WH, Willis WD (1976) Receptive fields of unmyelinated ventral root afferent fibres in the cat. J Physiol 256(3):573–600
Coggeshall R (1979) Afferent fibers in the ventral root. Neurosurgery 4(5):443–448
Danner SM, Zhang H, Shevtsova NA, Borowska-Fielding J, Deska-Gauthier D, Rybak IA, Zhang Y (2019) Spinal V3 interneurons and left-right coordination in mammalian locomotion. Front Cell Neurosci 13:516
Dougherty KJ, Zagoraiou L, Satoh D, Rozani I, Doobar S, Arber S, Jessell TM, Kiehn O (2013) Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons. Neuron 80(4):920–933
Eklof-Ljunggren E, Haupt S, Ausborn J, Dehnisch I, Uhlen P, Higashijima S, El Manira A (2012) Origin of excitation underlying locomotion in the spinal circuit of zebrafish. Proc Natl Acad Sci U S A 109(14):5511–5516
El-Gaby M, Zhang Y, Wolf K, Schwiening J, Christof OP, Shipton A, Olivia (2016) Archaerhodopsin selectively and reversibly silences synaptic transmission through altered pH. Cell Rep 16(8):2259–2268
Enjin A, Perry S, Hilscher MM, Nagaraja C, Larhammar M, Gezelius H, Eriksson A, Leao KE, Kullander K (2017) Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell-motor neuron circuit. J Neurosci 37(23):5634–5647
Falgairolle M, Puhl JG, Pujala A, Liu W, O’Donovan MJ (2017) Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse. elife 6
Gabriel JP, Mahmood R, Walter AM, Kyriakatos A, Hauptmann G, Calabrese RL, El Manira A (2008) Locomotor pattern in the adult zebrafish spinal cord in vitro. J Neurophysiol 99(1):37–48
Grillner S, Wallén P (1980) Does the central pattern generation for locomotion in lamprey depend on glycine inhibition? Acta Physiol Scand 110(1):103–105
Grillner S, Zangger P (1979) On the central generation of locomotion in the low spinal cat. Exp Brain Res 34(2)
Hall BK, Herring SW (1990) Paralysis and growth of the musculoskeletal system in the embryonic chick. J Morphol 206(1):45–56
Hamburger V (1990) The developmental history of the motor neuron. Neuroembryology 15:1–37
Hanson MG, Landmesser LT (2003) Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord. J Neurosci 23(2):587–600
Hanson MG, Landmesser LT (2004) Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. Neuron 43(5):687–701
Hildebrand C, Karlsson M, Risling M (1997) Ganglionic axons in motor roots and PIA mater. Prog Neurobiol 51(2):89–128
Hinckley CA, Hartley R, Wu L, Todd A, Ziskind-Conhaim, L (2005) Locomotor-Like Rhythms in a Genetically Distinct Cluster of Interneurons in the Mammalian Spinal Cord. J Neurophysiol 93(3):1439–1449. https://doi.org/10.1152/jn.00647.2004
Humphreys JM, Whelan PJ (2012) Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse. J Neurophysiol 108(12):3370–3381
Iles JF, Nicolopoulos-Stournaras S (1996) Fictive locomotion in the adult decerebrate rat. Exp Brain Res 109(3):393–398
Jiang Z, Carlin KP, Brownstone RM (1999) An in vitro functionally mature mouse spinal cord preparation for the study of spinal motor networks. Brain Res 816(2):493–499
Kiehn O, Iizuka M, Kudo N (1992) Resetting from low threshold afferents of N-methyl-D-aspartate-induced locomotor rhythm in the isolated spinal cord-hindlimb preparation from newborn rats. Neurosci Lett 148(1-2):43–46
Kudo N, Yamada T (1987) locomotor activity in a spinal cord-indlimb muscles preparation of the newborn rat studied in vitro. Neurosci Lett 75(1):43–48
Kwan AC, Dietz SB, Webb WW, Harris-Warrick RM (2009) Activity of Hb9 interneurons during fictive locomotion in mouse spinal cord. J Neurosci 29(37):11601–11613
Landmesser LT, O’Donovan MJ (1984) Activation patterns of embryonic chick hind limb muscles recorded in ovo and in an isolated spinal cord preparation. J Physiol 347(1):189–204
Lawton KJ, Perry WM, Yamaguchi A, Zornik E (2017) Motor neurons tune premotor activity in a vertebrate central pattern generator. J Neurosci 37(12):3264–3275
Li WC, Soffe SR, Roberts A (2004) Glutamate and acetylcholine corelease at developing synapses. Proc Natl Acad Sci U S A 101(43):15488–15493
Light AR, Metz CB (1978) The morphology of the spinal cord efferent and afferent neurons contributing to the ventral roots of the cat. J Comp Neurol 179(3):501–515
Machacek DW, Hochman S (2006) Noradrenaline unmasks novel self-reinforcing motor circuits within the mammalian spinal cord. J Neurosci 26(22):5920–5928
MacLean JN, Schmidt BJ, Hochman S (1997) NMDA receptor activation triggers voltage oscillations, plateau potentials and bursting in neonatal rat lumbar motoneurons in vitro. Eur J Neurosci 9(12):2702–2711
Manuel M, Li Y, Elbasiouny SM, Murray K, Griener A, Heckman CJ, Bennett DJ (2012) NMDA induces persistent inward and outward currents that cause rhythmic bursting in adult rodent motoneurons. J Neurophysiol 108(11):2991–2998
Mawe GM, Bresnahan JC, Beattie MS (1984) Primary afferent projections from dorsal and ventral roots to autonomic preganglionic neurons in the cat sacral spinal cord: light and electron microscopic observations. Brain Res 290(1):152–157
Maynard CW, Leonard RB, Dan Coulter J, Coggeshall RE (1977) Central connections of ventral root afferents as demonstrated by the HRP method. J Comp Neurol 172(4):601–608
Meehan CF, Grondahl L, Nielsen JB, Hultborn H (2012) Fictive locomotion in the adult decerebrate and spinal mouse in vivo. J Physiol 590(2):289–300
Mentis GZ, Alvarez FJ, Bonnot A, Richards DS, Gonzalez-Forero D, Zerda R, O’Donovan MJ (2005) Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. Proc Natl Acad Sci U S A 102(20):7344–7349
Milner LD, Landmesser LT (1999) Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. J Neurosci 19(8):3007–3022
Nakanishi ST, Whelan PJ (2012) A decerebrate adult mouse model for examining the sensorimotor control of locomotion. J Neurophysiol 107(1):500–515
Nishimaru H, Restrepo CE, Ryge J, Yanagawa Y, Kiehn O (2005) Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. Proc Natl Acad Sci U S A 102(14):5245–5249
O’Donovan M, Ho S, Yee W (1994) Calcium imaging of rhythmic network activity in the developing spinal cord of the chick embryo. J Neurosci 14(11 Pt 1):6354–6369
Perrins R, Roberts A (1995) Cholinergic contribution to excitation in a spinal locomotor central pattern generator in Xenopus embryos. J Neurophysiol 73(3):1013–1019
Pham BN, Luo J, Anand H, Kola O, Salcedo P, Nguyen C, Gaunt S, Zhong H, Garfinkel A, Tillakaratne N, Edgerton VR (2020) Redundancy and multifunctionality among spinal locomotor networks. J Neurophysiol 124(5):1469–1479
Popa LS, Ebner TJ (2018) Cerebellum, predictions and errors. Front Cell Neurosci 12:524
Pratt CA, Jordan LM (1987) Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion. J Neurophysiol 57(1):56–71
Provine RR, Sharma SC, Sandel TT, Hamburger V (1970) Electrical activity in the spinal cord of the chick embryo, in situ. Proc Natl Acad Sci 65(3):508–515
Pujala A, Blivis D, O’Donovan MJ (2016) Interactions between dorsal and ventral root stimulation on the generation of locomotor-like activity in the neonatal mouse spinal cord. eneuro 3(3):ENEURO.0101-0116
Rancic V, Ballanyi K, Gosgnach S (2020) Mapping the dynamic recruitment of spinal neurons during fictive locomotion. J Neurosci 40(50):9692–9700
Richards DS, Griffith RW, Romer SH, Alvarez FJ (2014) Motor axon synapses on Renshaw cells contain higher levels of aspartate than glutamate. PLoS One 9(5):e97240
Shin HK, Kim J, Nam SC, Paik KS, Chung JM (1986) Spinal entry route for ventral root afferent fibers in the cat. Exp Neurol 94(3):714–725
Smith JC, Feldman JL (1987) In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion. J Neurosci Methods 21(2-4):321–333
Song J, Ampatzis K, Bjornfors ER, El Manira A (2016) Motor neurons control locomotor circuit function retrogradely via gap junctions. Nature 529(7586):399–402
Talpalar AE, Endo T, Low P, Borgius L, Hagglund M, Dougherty KJ, Ryge J, Hnasko TS, Kiehn O (2011) Identification of minimal neuronal networks involved in flexor-extensor alternation in the mammalian spinal cord. Neuron 71(6):1071–1084
Toutant JP, Toutant MN, Renaud D, Le Douarin GH (1979) Enzymatic differentiation of muscle fibre types in embryonic Latissimus dorsii of the chick: effects of spinal cord stimulation. Cell Diff 8(5):375–382
Viala D, Buser P (1969) The effects of DOPA and 5-HTP on rhythmic efferent discharges in hind limb nerves in the rabbit. Brain Res 12(2):437–443
Wallen PLA (1984) Do the motoneurones constitute a part of the spinal network generating the Swimming rhythm in the lamprey? J Exp Biol 113(November):493–497
Wenner P (2014) Homeostatic synaptic plasticity in developing spinal networks driven by excitatory GABAergic currents. Neuropharmacology 78:55–62
Wenner P, O’Donovan MJ (1999) Identification of an interneuronal population that mediates recurrent inhibition of motoneurons in the developing chick spinal cord. J Neurosci 19(17):7557–7567
Wenner P, O’Donovan MJ (2001) Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. J Neurophysiol 86(3):1481–1498
Whelan P, Bonnot A, O’Donovan MJ (2000) Properties of rhythmic activity generated by the isolated spinal cord of the neonatal mouse. J Neurophysiol 84(6):2821–2833
Wilson JM, Hartley R, Maxwell DJ, Todd AJ, Lieberam I, Kaltschmidt JA, Yoshida Y, Jessell TM, Brownstone RM (2005) Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. J Neurosci 25(24):5710–5719
Windle WF (1931) Neurons of the sensory type in the ventral roots of man and of other mammals. Arch Neurol Psychiatr 26(4):791
Wolpert DM, Miall RC (1996) Forward models for physiological motor control. Neural Netw 9(8):1265–1279
Yamamoto T, Takahashi K, Satomi H, Ise H (1977) Origins of primary afferent fibers in the spinal ventral roots in the cat as demonstrated by the horseradish peroxidase method. Brain Res 126(2):350–354
Zaporozhets E, Cowley KC, Schmidt BJ (2004) A reliable technique for the induction of locomotor-like activity in the in vitro neonatal rat spinal cord using brainstem electrical stimulation. J Neurosci Methods 139(1):33–41
Zhang F, Wang L-P, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A, Deisseroth K (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446(7136):633–639
Zhang Y, Narayan S, Geiman E, Lanuza GM, Velasquez T, Shanks B, Akay T, Dyck J, Pearson K, Gosgnach S, Fan CM, Goulding M (2008) V3 spinal neurons establish a robust and balanced locomotor rhythm during walking. Neuron 60(1):84–96
Zornik E, Yamaguchi A (2012) Coding rate and duration of vocalizations of the frog, Xenopus laevis. J Neurosci 32(35):12102–12114
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Falgairolle, M., O’Donovan, M.J. (2022). Motoneuronal Regulation of Central Pattern Generator and Network Function. In: O'Donovan, M.J., Falgairolle, M. (eds) Vertebrate Motoneurons. Advances in Neurobiology, vol 28. Springer, Cham. https://doi.org/10.1007/978-3-031-07167-6_11
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