Formation of the central pattern generator for locomotion in the rat and mouse

It is well known that in the neonatal rat spinal cord preparation, alternating rhythmic bursts in the left and right ventral roots in a given lumbar segment can be induced by bath-application of N-methyl-D-aspartate or 5-hydroxytryptamine. Alternation between L2 and L5 ventral roots on the same side, representing the activity of flexor and extensor muscles, respectively, can be observed as well. In the prenatal period in the rat, alternation between the left and right ventral roots is established between embryonic day (E) 16.5 and E18.5. The alternation between the L2 and L5 ventral roots emerges at E20.5. Recent findings show that locomotor-like rhythmic activity with similar characteristics can be induced in the neonatal mouse preparation. In the lumbar spinal cord in the neonatal mouse, it is likely that the rhythm-generating network is distributed throughout the lumbar region with a rostro-caudal gradient, a situation similar to that in the neonatal and fetal rat spinal cord. With this review we hope to highlight the dramatic changes that neuronal networks generating locomotor-like activity undergo during the prenatal development of the rat. Moreover, the distribution of the neuronal network generating the locomotor rhythm in the neonatal rat and mouse spinal cord is compared.

[1]  O Kiehn,et al.  Coding of locomotor phase in populations of neurons in rostral and caudal segments of the neonatal rat lumbar spinal cord. , 1999, Journal of neurophysiology.

[2]  V. Hamburger,et al.  Prenatal development of spontaneous and evoked activity in the rat (Rattus norvegicus albinus). , 1971, Behaviour.

[3]  A. Lev-Tov,et al.  Localization of the spinal network associated with generation of hindlimb locomotion in the neonatal rat and organization of its transverse coupling system. , 1997, Journal of neurophysiology.

[4]  O. Kiehn,et al.  Spatiotemporal characteristics of 5-HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat. , 1996, Journal of neurophysiology.

[5]  R. Brownstone,et al.  An in vitro functionally mature mouse spinal cord preparation for the study of spinal motor networks , 1999, Brain Research.

[6]  S. Charpak,et al.  Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons. , 1998, Journal of neurophysiology.

[7]  F. Clarac,et al.  Spontaneous and locomotor‐related GABAergic input onto primary afferents in the neonatal rat , 2000, The European journal of neuroscience.

[8]  N. Dale,et al.  Experimentally derived model for the locomotor pattern generator in the Xenopus embryo. , 1995, The Journal of physiology.

[9]  W D Snider,et al.  Development of commissural neurons in the embryonic rat spinal cord , 1992, The Journal of comparative neurology.

[10]  F. Clarac,et al.  Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat. , 1992, The Journal of physiology.

[11]  L. Kempe Handbook of Physiology. Section I. The Nervous System , 1982 .

[12]  B J Schmidt,et al.  Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord. , 1995, Journal of neurophysiology.

[13]  P. Jonas,et al.  Corelease of two fast neurotransmitters at a central synapse. , 1998, Science.

[14]  A. Roberts,et al.  Experiments on the central pattern generator for swimming in amphibian embryos. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[15]  N. Kudo,et al.  Rostrocaudal progression in the development of periodic spontaneous activity in fetal rat spinal motor circuits in vitro. , 1999, Journal of neurophysiology.

[16]  D. Stehouwer,et al.  L-dopa-induced air-stepping in developing rats. , 1991, Brain research. Developmental brain research.

[17]  O. Kiehn,et al.  Development in neonatal rats of the sensory resetting of the locomotor rhythm induced by NMDA and 5-HT , 1997, Experimental Brain Research.

[18]  L Ziskind-Conhaim,et al.  Development of glycine- and GABA-gated currents in rat spinal motoneurons. , 1995, Journal of neurophysiology.

[19]  T. Suzue Physiological activities of late-gestation rat fetuses in vitro , 1992, Neuroscience Research.

[20]  K. Sillar,et al.  Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord. , 1999, Journal of neurophysiology.

[21]  S. Grillner Neurobiological bases of rhythmic motor acts in vertebrates. , 1985, Science.

[22]  Michael J. O'Donovan,et al.  Regionalization and intersegmental coordination of rhythm-generating networks in the spinal cord of the chick embryo , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  L. Ballerini,et al.  Spontaneous rhythmic bursts induced by pharmacological block of inhibition in lumbar motoneurons of the neonatal rat spinal cord. , 1996, Journal of neurophysiology.

[24]  D. Morin,et al.  Hemisegmental localisation of rhythmic networks in the lumbosacral spinal cord of neonate mouse , 1998, Brain Research.

[25]  S. Grillner Control of Locomotion in Bipeds, Tetrapods, and Fish , 1981 .

[26]  B J Schmidt,et al.  NMDA Receptor‐mediated Oscillatory Properties: Potential Role in Rhythm Generation in the Mammalian Spinal Cord , 1998, Annals of the New York Academy of Sciences.

[27]  F. Clarac,et al.  Gabaergic Control of Spinal Locomotor Networks in the Neonatal Rat , 1998, Annals of the New York Academy of Sciences.

[28]  M. Jackson,et al.  Early development of glycine- and GABA-mediated synapses in rat spinal cord , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  K. Sillar,et al.  Modulation of swimming rhythmicity by 5-hydroxytryptamine during post-embryonic development in Xenopus laevis , 1992, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[30]  J. A. Payne,et al.  The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation , 1999, Nature.

[31]  F. Clarac,et al.  Antidromic discharges of dorsal root afferents in the neonatal rat , 1999, Journal of Physiology-Paris.

[32]  N. Kudo,et al.  Development of locomotor activity induced by NMDA receptor activation in the lumbar spinal cord of the rat fetus studied in vitro. , 1996, Brain research. Developmental brain research.

[33]  N. Kudo,et al.  Development of the spatial pattern of 5-HT-induced locomotor rhythm in the lumbar spinal cord of rat fetuses in vitro , 1998, Neuroscience Research.

[34]  M. Geffard,et al.  Pre‐ and post‐natal ontogeny of serotonergic projections to the rat spinal cord , 1989, Journal of neuroscience research.

[35]  J. Westerga,et al.  The development of locomotion in the rat. , 1990, Brain research. Developmental brain research.

[36]  B. Schmidt,et al.  Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. , 1997, Journal of neurophysiology.

[37]  S. Grillner,et al.  The neural network underlying locomotion in lamprey-synaptic and cellular mechanisms , 1991, Neuron.

[38]  N. Kudo,et al.  N-Methyl-d,l-aspartate-induced locomotor activity in a spinal cord-indlimb muscles preparation of the newborn rat studied in vitro , 1987, Neuroscience Letters.

[39]  N. Kudo,et al.  5-Hydroxytryptamine-induced locomotor rhythm in the neonatal mouse spinal cord in vitro , 2000, Neuroscience Letters.

[40]  J. Iles,et al.  Motor neuron columns in the lumbar spinal cord of the rat , 1983, The Journal of comparative neurology.

[41]  M. Pinter,et al.  Gap Junctional Coupling and Patterns of Connexin Expression among Neonatal Rat Lumbar Spinal Motor Neurons , 1999, The Journal of Neuroscience.

[42]  B. Seebach,et al.  Changes in serotonin-induced potentials during spinal cord development. , 1993, Journal of neurophysiology.

[43]  S. Soffe Ionic and pharmacological properties of reciprocal inhibition in Xenopus embryo motoneurones. , 1987, The Journal of physiology.

[44]  G. Owens,et al.  Ontogeny of cation-Cl- cotransporter expression in rat neocortex. , 1998, Brain research. Developmental brain research.

[45]  S. Mori,et al.  Prenatal administration of para-chlorophenylalanine results in suppression of serotonergic system and disturbance of swimming movements in newborn rats , 1998, Neuroscience Research.

[46]  O Kiehn,et al.  Distribution of Networks Generating and Coordinating Locomotor Activity in the Neonatal Rat Spinal Cord In Vitro: A Lesion Study , 1996, The Journal of Neuroscience.

[47]  J. Barker,et al.  Transient expression of GABA immunoreactivity in the developing rat spinal cord , 1992, The Journal of comparative neurology.

[48]  L. Ballerini,et al.  Localization of Rhythmogenic Networks Responsible for Spontaneous Bursts Induced by Strychnine and Bicuculline in the Rat Isolated Spinal Cord , 1996, The Journal of Neuroscience.

[49]  A. Bekoff,et al.  Interlimb coordination in 20-day-old rat fetuses. , 1980, The Journal of experimental zoology.

[50]  O. Kiehn,et al.  Distribution of Central Pattern Generators for Rhythmic Motor Outputs in the Spinal Cord of Limbed Vertebrates a , 1998, Annals of the New York Academy of Sciences.

[51]  R. Oppenheim The absence of significant postnatal motoneuron death in the brachial and lumbar spinal cord of the rat , 1986, The Journal of comparative neurology.

[52]  Jack L. Feldman,et al.  In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion , 1987, Journal of Neuroscience Methods.

[53]  N. Kudo,et al.  Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro. , 1996, The Journal of physiology.

[54]  P. Phelps,et al.  Ventrally located commissural neurons express the GABAergic phenotype in developing rat spinal cord , 1999, The Journal of comparative neurology.

[55]  S. Grillner Locomotion in vertebrates: central mechanisms and reflex interaction. , 1975, Physiological reviews.

[56]  K. Saito,et al.  Development of spinal reflexes in the rat fetus studied in vitro. , 1979, The Journal of physiology.

[57]  N. Akaike,et al.  Regulation of Intracellular Chloride by Cotransporters in Developing Lateral Superior Olive Neurons , 1999, The Journal of Neuroscience.

[58]  B. Schmidt,et al.  A comparison of motor patterns induced by N-methyl-d-aspartate , acetylcholine and serotonin in the in vitro neonatal rat spinal cord , 1994, Neuroscience Letters.

[59]  N. Kudo,et al.  Reorganization of Locomotor Activity during Development in the Prenatal Rata , 1998, Annals of the New York Academy of Sciences.

[60]  O Kiehn,et al.  Crossed Rhythmic Synaptic Input to Motoneurons during Selective Activation of the Contralateral Spinal Locomotor Network , 1997, The Journal of Neuroscience.

[61]  F. Clarac,et al.  Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[62]  N. Spitzer,et al.  Regulation of intracellular Cl- levels by Na(+)-dependent Cl- cotransport distinguishes depolarizing from hyperpolarizing GABAA receptor-mediated responses in spinal neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.