Multiple spontaneous rhythmic activity patterns generated by the embryonic mouse spinal cord occur within a specific developmental time window.

Spontaneous rhythmic activity is a ubiquitous phenomenon in developing neural networks and is assumed to play an important role in the elaboration of mature circuitry. Here we describe the day-by-day evolution of spontaneous activity in the embryonic mouse spinal cord and show that, at a specific developmental stage, 2 distinct rhythms coexist. On embryonic days E12.5 and E13.5, we observed a single type of regularly recurring short spike-episodes synchronized across cervical, thoracic, and lumbar levels. By E14.5, in addition to this motor rhythm, another type of spontaneous synchronous activity appeared, characterized by much longer lasting episodes separated by longer time intervals. On E15.5, these long episodes disappeared. Short episodes were less numerous and more irregular except at the cervical level where a rhythm was occasionally observed. By E16.5, this cervical rhythm became more robust, whereas the lumbar level fell almost silent. Surprisingly, at E17.5, spontaneous activity resumed at caudal levels, now characterized by numerous erratic short episodes. A striking ontogenetic feature of spontaneous activity was the occurrence of long episodes only at E14.5. Although concomitant at all levels of the spinal cord, long episodes displayed different patterns along the spinal cord, with tonic firing at the thoracic level and rhythmic discharge with occasional sequences of left/right alternation at the lumbar level. Thus at E14.5, the originally synchronized network has started to segregate into more specialized subnetworks. In conclusion, this work suggests that ongoing spontaneous rhythms do not follow a smooth evolution during maturation, but rather undergo profound changes at very specific stages.

[1]  N. Kudo,et al.  Developmental changes in 5-hydroxytryptamine-induced rhythmic activity in the spinal cord of rat fetuses in vitro , 2001, Neuroscience Letters.

[2]  M. Hanson,et al.  Characterization of the Circuits That Generate Spontaneous Episodes of Activity in the Early Embryonic Mouse Spinal Cord , 2003, The Journal of Neuroscience.

[3]  C. Shatz Emergence of order in visual system development. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  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.

[5]  N. Kudo,et al.  Basis of Changes in Left–Right Coordination of Rhythmic Motor Activity during Development in the Rat Spinal Cord , 2002, The Journal of Neuroscience.

[6]  C. Shatz,et al.  Brain Waves and Brain Wiring: The Role of Endogenous and Sensory-Driven Neural Activity in Development , 1999, Pediatric Research.

[7]  Michael J. O'Donovan,et al.  Modeling of Spontaneous Activity in Developing Spinal Cord Using Activity-Dependent Depression in an Excitatory Network , 2000, The Journal of Neuroscience.

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

[9]  Hiroshi Nishimaru,et al.  Formation of the central pattern generator for locomotion in the rat and mouse , 2000, Brain Research Bulletin.

[10]  Michael J. O'Donovan The origin of spontaneous activity in developing networks of the vertebrate nervous system , 1999, Current Opinion in Neurobiology.

[11]  Michael J. O'Donovan,et al.  Properties of rhythmic activity generated by the isolated spinal cord of the neonatal mouse. , 2000, Journal of neurophysiology.

[12]  J. Greer,et al.  Ontogeny of rhythmic motor patterns generated in the embryonic rat spinal cord. , 2003, Journal of neurophysiology.

[13]  M. Geffard,et al.  Pre- and postnatal development of noradrenergic projections to the rat spinal cord: an immunocytochemical study. , 1992, Brain research. Developmental brain research.

[14]  E. Lakke The Projections to the Spinal Cord of the Rat During Development: A Timetable of Descent , 1997, Advances in Anatomy Embryology and Cell Biology.

[15]  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.

[16]  N. Spitzer,et al.  Regulation of growth cone behavior by calcium: new dynamics to earlier perspectives. , 2000, Journal of neurobiology.

[17]  Michael J. O'Donovan,et al.  Mechanisms of spontaneous activity in developing spinal networks. , 1998, Journal of neurobiology.

[18]  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.

[19]  L. Landmesser,et al.  Cholinergic and GABAergic Inputs Drive Patterned Spontaneous Motoneuron Activity before Target Contact , 1999, The Journal of Neuroscience.

[20]  Michael J. O'Donovan,et al.  Spatiotemporal Pattern of Motoneuron Activation in the Rostral Lumbar and the Sacral Segments during Locomotor-Like Activity in the Neonatal Mouse Spinal Cord , 2002, The Journal of Neuroscience.

[21]  P. Branchereau,et al.  Development of lumbar rhythmic networks: from embryonic to neonate locomotor-like patterns in the mouse , 2000, Brain Research Bulletin.

[22]  P. Branchereau,et al.  Descending 5-Hydroxytryptamine Raphe Inputs Repress the Expression of Serotonergic Neurons and Slow the Maturation of Inhibitory Systems in Mouse Embryonic Spinal Cord , 2002, The Journal of Neuroscience.

[23]  Michael J. O'Donovan,et al.  The Role of Activity-Dependent Network Depression in the Expression and Self-Regulation of Spontaneous Activity in the Developing Spinal Cord , 2001, The Journal of Neuroscience.

[24]  Y. Ben-Ari Developing networks play a similar melody , 2001, Trends in Neurosciences.

[25]  R. Wong,et al.  Developmental Loss of Synchronous Spontaneous Activity in the Mouse Retina Is Independent of Visual Experience , 2003, The Journal of Neuroscience.

[26]  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.

[27]  P. Branchereau,et al.  Ontogeny of descending serotonergic innervation and evidence for intraspinal 5-HT neurons in the mouse spinal cord. , 2002, Brain research. Developmental brain research.

[28]  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.

[29]  Michael J. O'Donovan,et al.  Locomotor-like activity generated by the neonatal mouse spinal cord , 2002, Brain Research Reviews.