Endogenous Patterns of Activity Are Required for the Maturation of a Motor Network

Many parts of the nervous system become active before development is complete, including the embryonic spinal cord. Remarkably, although the subject has been debated for over a century (Harrison, 1904), it is still unclear whether such activity is required for normal development of motor circuitry. In Drosophila, embryonic motor output is initially poorly organized, and coordinated crawling-like behavior gradually emerges over the subsequent phase of development. We show that reversibly blocking synaptic transmission during this phase severely delays the first appearance of coordinated movements. When we interfere with the pattern of neuronal firing during this period, coordination is also delayed or blocked. We conclude that there is a period during which endogenous patterns of neuronal activity are required for the normal development of motor circuits in Drosophila.

[1]  M. Burrows.  The morphology of an elevator and a depressor motoneuron of the hindwing of a locust , 1973, Journal of comparative physiology.

[2]  Matthias Landgraf,et al.  Structural Homeostasis: Compensatory Adjustments of Dendritic Arbor Geometry in Response to Variations of Synaptic Input , 2008, PLoS biology.

[3]  M. D. Ross Granville Harrison,et al.  An experimental study of the relation of the nervous system to the developing musculature in the embryo of the frog , 1904 .

[4]  E. Marder,et al.  Activity-Dependent Regulation of Potassium Currents in an Identified Neuron of the Stomatogastric Ganglion of the Crab Cancer borealis , 1999, The Journal of Neuroscience.

[5]  C. Goodman.  Isogenic grasshoppers: Genetic variability in the morphology of identified neurons , 1978, The Journal of comparative neurology.

[6]  K. Pearson,et al.  Correlation of variability in structure with variability in synaptic connections of an identified interneuron in locusts , 1979, The Journal of comparative neurology.

[7]  M. Feller,et al.  Mechanisms underlying spontaneous patterned activity in developing neural circuits , 2010, Nature Reviews Neuroscience.

[8]  D. O'Leary,et al.  Retinotopic Map Refinement Requires Spontaneous Retinal Waves during a Brief Critical Period of Development , 2003, Neuron.

[9]  M. Suster,et al.  Embryonic assembly of a central pattern generator without sensory input , 2002, Nature.

[10]  Alexander Sher,et al.  Spatial-Temporal Patterns of Retinal Waves Underlying Activity-Dependent Refinement of Retinofugal Projections , 2009, Neuron.

[11]  W. Kristan,et al.  Development of spontaneous and evoked behaviors in the medicinal leech , 1998, The Journal of comparative neurology.

[12]  Michael Bate,et al.  Electrophysiological Development of Central Neurons in theDrosophila Embryo , 1998, The Journal of Neuroscience.

[13]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[14]  Nicholas C. Spitzer,et al.  Activity-dependent homeostatic specification of transmitter expression in embryonic neurons , 2004, Nature.

[15]  S. Schmid,et al.  Analysis of the Activity-Deprived Zebrafish Mutantmacho Reveals an Essential Requirement of Neuronal Activity for the Development of a Fine-Grained Visuotopic Map , 2001, The Journal of Neuroscience.

[16]  M. Keating,et al.  Synchronizing Retinal Activity in Both Eyes Disrupts Binocular Map Development in the Optic Tectum , 1998, The Journal of Neuroscience.

[17]  H. Aberle,et al.  The expression pattern of the Drosophila vesicular glutamate transporter: a marker protein for motoneurons and glutamatergic centers in the brain. , 2006, Gene expression patterns : GEP.

[18]  E. Marder,et al.  Activity-dependent modification of inhibitory synapses in models of rhythmic neural networks , 2001, Nature Neuroscience.

[19]  T. Kitamoto.  Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. , 2001, Journal of neurobiology.

[20]  Fred H. Gage,et al.  Cholinergic Input Is Required during Embryonic Development to Mediate Proper Assembly of Spinal Locomotor Circuits , 2005, Neuron.

[21]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[22]  H. Nakamura,et al.  Disturbance of refinement of retinotectal projection in chick embryos by tetrodotoxin and grayanotoxin. , 1990, Brain research. Developmental brain research.

[23]  A. Roberts,et al.  How Neurons Generate Behavior in A Hatchling Amphibian Tadpole: An Outline , 2010, Front. Behav. Neurosci..

[24]  C. Levinthal,et al.  Anatomy and development of identified cells in isogenic organisms. , 1976, Cold Spring Harbor symposia on quantitative biology.

[25]  P. Drapeau,et al.  Time course of the development of motor behaviors in the zebrafish embryo. , 1998, Journal of neurobiology.

[26]  Jan Felix Evers,et al.  The development of motor coordination in Drosophila embryos , 2008, Development.

[27]  F. Clarac,et al.  The in vitro neonatal rat spinal cord preparation: a new insight into mammalian locomotor mechanisms , 2004, Journal of Comparative Physiology A.

[28]  M. Goulding.  Circuits controlling vertebrate locomotion: moving in a new direction , 2009, Nature Reviews Neuroscience.

[29]  E. Marder,et al.  Similar network activity from disparate circuit parameters , 2004, Nature Neuroscience.

[30]  William A. Harris,et al.  [Development of the nervous system]. , 2000, Ceskoslovenska fysiologie.

[31]  L. Haverkamp,et al.  Anatomical and physiological development of the Xenopus embryonic motor system in the absence of neural activity , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  R. Baines.  Postsynaptic Protein Kinase A Reduces Neuronal Excitability in Response to Increased Synaptic Excitation in the Drosophila CNS , 2003, The Journal of Neuroscience.

[33]  L. Landmesser,et al.  In Vivo Activation of Channelrhodopsin-2 Reveals That Normal Patterns of Spontaneous Activity Are Required for Motoneuron Guidance and Maintenance of Guidance Molecules , 2010, The Journal of Neuroscience.

[34]  Michael J. O'Donovan,et al.  Activation patterns of embryonic chick hind limb muscles recorded in ovo and in an isolated spinal cord preparation. , 1984, The Journal of physiology.

[35]  G. Davis,et al.  Drosophila Futsch/22C10 Is a MAP1B-like Protein Required for Dendritic and Axonal Development , 2000, Neuron.

[36]  J. Schmidt,et al.  Activity-driven sharpening of the retinotectal projection in goldfish: development under stroboscopic illumination prevents sharpening. , 1993, Journal of neurobiology.

[37]  William A. Harris,et al.  Development of the Nervous System Ed. 3 , 2011 .

[38]  A. Roberts,et al.  Development of early swimming inXenopus laevis embryos: Myotomal musculature, its innervation and activation , 1989, Neuroscience.

[39]  R. Oppenheim,et al.  Behavioral development in the absence of neural activity: effects of chronic immobilization on amphibian embryos , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  C. Stuermer,et al.  Growth behavior of retinotectal axons in live zebrafish embryos under TTX-induced neural impulse blockade. , 1994, Journal of neurobiology.

[41]  G. Nagel,et al.  Light-Induced Activation of Distinct Modulatory Neurons Triggers Appetitive or Aversive Learning in Drosophila Larvae , 2006, Current Biology.

[42]  Michael Bate,et al.  Altered Electrical Properties in DrosophilaNeurons Developing without Synaptic Transmission , 2001, The Journal of Neuroscience.