Assembly of Motor Circuits in the Spinal Cord: Driven to Function by Genetic and Experience-Dependent Mechanisms

Motor circuits in the spinal cord integrate information from various sensory and descending pathways to control appropriate motor behavior. Recent work has revealed that target-derived retrograde signaling mechanisms act to influence sequential assembly of motor circuits through combinatorial action of genetic and experience-driven programs. These parallel activities imprint somatotopic information at the level of the spinal cord in precisely interconnected circuits and equip animals with motor circuits capable of reacting to changing demands throughout life.

[1]  Jane E. Johnson,et al.  Specification of dorsal spinal cord interneurons , 2003, Current Opinion in Neurobiology.

[2]  M. Goulding,et al.  Postnatal phenotype and localization of spinal cord V1 derived interneurons , 2005, The Journal of comparative neurology.

[3]  J. Milbrandt,et al.  Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3 , 1998, Nature Genetics.

[4]  Vincenzo De Paola,et al.  ETS Gene Pea3 Controls the Central Position and Terminal Arborization of Specific Motor Neuron Pools , 2002, Neuron.

[5]  T. Jessell,et al.  Genetic Identification of Spinal Interneurons that Coordinate Left-Right Locomotor Activity Necessary for Walking Movements , 2004, Neuron.

[6]  Peter Wenner,et al.  Spontaneous Network Activity in the Embryonic Spinal Cord Regulates AMPAergic and GABAergic Synaptic Strength , 2006, Neuron.

[7]  Ian R. Wickersham,et al.  Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons , 2007, Neuron.

[8]  R. Harris-Warrick,et al.  The evolution of neuronal circuits underlying species-specific behavior , 1999, Current Opinion in Neurobiology.

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

[10]  U. Windhorst,et al.  Activation of renshaw cells , 1990, Progress in Neurobiology.

[11]  C. Straznicky,et al.  The localization of motoneuron pools innervating wing muscles in the chick , 2004, Anatomy and Embryology.

[12]  G. Rousseau,et al.  Retrograde BMP Signaling Regulates Trigeminal Sensory Neuron Identities and the Formation of Precise Face Maps , 2007, Neuron.

[13]  G. Grande,et al.  Distribution of contacts from vestibulospinal axons on the dendrites of splenius motoneurons , 2005, The Journal of comparative neurology.

[14]  S. Arber,et al.  A Role for Runx Transcription Factor Signaling in Dorsal Root Ganglion Sensory Neuron Diversification , 2006, Neuron.

[15]  L. Zon,et al.  Notch and MAML Signaling Drives Scl-Dependent Interneuron Diversity in the Spinal Cord , 2007, Neuron.

[16]  R E Burke,et al.  Horseradish peroxidase study of the spatial and electrotonic distribution of group Ia synapses on type‐identified ankle extensor motoneurons in the cat , 1996, The Journal of comparative neurology.

[17]  S. Arber,et al.  Peripheral NT3 Signaling Is Required for ETS Protein Expression and Central Patterning of Proprioceptive Sensory Afferents , 2003, Neuron.

[18]  Michael J. O'Donovan,et al.  Topographical and physiological characterization of interneurons that express engrailed-1 in the embryonic chick spinal cord. , 2000, Journal of neurophysiology.

[19]  R. Fyffe,et al.  Spinal Motoneurons: Synaptic Inputs and Receptor Organization , 2001 .

[20]  T. Jessell,et al.  Runx1 Determines Nociceptive Sensory Neuron Phenotype and Is Required for Thermal and Neuropathic Pain , 2006, Neuron.

[21]  M. Goulding,et al.  Development of circuits that generate simple rhythmic behaviors in vertebrates , 2005, Current Opinion in Neurobiology.

[22]  G. Romanes,et al.  The motor cell columns of the lumbo‐sacral spinal cord of the cat , 1951, The Journal of comparative neurology.

[23]  T. Jessell.  Neuronal specification in the spinal cord: inductive signals and transcriptional codes , 2000, Nature Reviews Genetics.

[24]  R. Brownstone,et al.  Postnatal development of cholinergic synapses on mouse spinal motoneurons , 2004, The Journal of comparative neurology.

[25]  J Schouenborg,et al.  Functional organization of the nociceptive withdrawal reflexes , 1992, Experimental Brain Research.

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

[27]  Sten Grillner,et al.  Biological Pattern Generation: The Cellular and Computational Logic of Networks in Motion , 2006, Neuron.

[28]  R. Lemon,et al.  Comparing the function of the corticospinal system in different species: Organizational differences for motor specialization? , 2005, Muscle & nerve.

[29]  Hans Holmberg,et al.  Spinal Sensorimotor Transformation: Relation between Cutaneous Somatotopy and a Reflex Network , 2002, The Journal of Neuroscience.

[30]  S. Arber,et al.  GDNF Acts through PEA3 to Regulate Cell Body Positioning and Muscle Innervation of Specific Motor Neuron Pools , 2002, Neuron.

[31]  H. Nornes,et al.  Neurogenesis in spinal cord of mouse: an autoradiographic analysis , 1978, Brain Research.

[32]  J. Wolpaw,et al.  Activity-dependent spinal cord plasticity in health and disease. , 2001, Annual review of neuroscience.

[33]  P. Wenner,et al.  Developmental reorganization of the output of a GABAergic interneuronal circuit. , 2007, Journal of neurophysiology.

[34]  S. Rossignol,et al.  Dynamic sensorimotor interactions in locomotion. , 2006, Physiological reviews.

[35]  S. Ozaki,et al.  Initial trajectories of sensory axons toward laminar targets in the developing mouse spinal cord , 1997, The Journal of comparative neurology.

[36]  J. Schouenborg,et al.  A survey of spinal dorsal horn neurones encoding the spatial organization of withdrawal reflexes in the rat , 2004, Experimental Brain Research.

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

[38]  S. Cullheim,et al.  Large cholinergic nerve terminals on subsets of motoneurons and their relation to muscarinic receptor type 2 , 2003, The Journal of comparative neurology.

[39]  Z. J. Huang,et al.  Subcellular organization of GABAergic synapses: role of ankyrins and L1 cell adhesion molecules , 2006, Nature Neuroscience.

[40]  U. Windhorst.  Muscle proprioceptive feedback and spinal networks , 2007, Brain Research Bulletin.

[41]  E. Frank,et al.  Development of central projections of lumbosacral sensory neurons in the chick , 1989, The Journal of comparative neurology.

[42]  J. Schouenborg.  Learning in sensorimotor circuits , 2004, Current Opinion in Neurobiology.

[43]  R. Fyffe,et al.  Spatial distribution of recurrent inhibitory synapses on spinal motoneurons in the cat. , 1991, Journal of neurophysiology.

[44]  E. Frank,et al.  Formation of Specific Monosynaptic Connections between Muscle Spindle Afferents and Motoneurons in the Mouse , 1997, The Journal of Neuroscience.

[45]  Jens Schouenborg,et al.  Modular organisation and spinal somatosensory imprinting , 2002, Brain Research Reviews.

[46]  A Levinsson,et al.  Developmental Tuning in a Spinal Nociceptive System: Effects of Neonatal Spinalization , 1999, The Journal of Neuroscience.

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

[48]  R. N. Lemon,et al.  An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: lack of evidence for cortico-motoneuronal synapses , 2003, Experimental Brain Research.

[49]  M. Goulding,et al.  Lbx1 Specifies Somatosensory Association Interneurons in the Dorsal Spinal Cord , 2002, Neuron.

[50]  Thomas M. Jessell,et al.  Motor neuron columnar fate imposed by sequential phases of Hox-c activity , 2003, Nature.

[51]  A. G. Brown,et al.  The dorsal horn of the spinal cord. , 1982, Quarterly journal of experimental physiology.

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

[53]  Michael J. O'Donovan,et al.  Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[54]  K. Ballanyi,et al.  Disruption of KCC2 Reveals an Essential Role of K-Cl Cotransport Already in Early Synaptic Inhibition , 2001, Neuron.

[55]  Jens Schouenborg,et al.  Spontaneous muscle twitches during sleep guide spinal self-organization , 2003, Nature.

[56]  P K Rose,et al.  Innervation of motoneurons based on dendritic orientation. , 1995, Journal of neurophysiology.

[57]  N. Okado,et al.  Distribution patterns of dendrites in motor neuron pools of lumbosacral spinal cord of the chicken , 2004, Anatomy and Embryology.

[58]  L M Mendell,et al.  Neurotrophins and synaptic plasticity in the mammalian spinal cord , 2001, The Journal of physiology.

[59]  A. Lev-Tov,et al.  The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons , 2002, The EMBO journal.

[60]  M. Woodin,et al.  Role of activity-dependent regulation of neuronal chloride homeostasis in development , 2007, Current Opinion in Neurobiology.

[61]  Silvia Arber,et al.  Target-Induced Transcriptional Control of Dendritic Patterning and Connectivity in Motor Neurons by the ETS Gene Pea3 , 2006, Cell.

[62]  A. Samuels,et al.  Topographic Position of Forelimb Motoneuron Pools Is Conserved in Vertebrate Evolution , 1998, Brain, Behavior and Evolution.

[63]  Timothy C. Cope,et al.  Motor Neurobiology of the Spinal Cord , 2001 .

[64]  A. G. Brown,et al.  Direct observations on the contacts made between Ia afferent fibres and alpha‐motoneurones in the cat's lumbosacral spinal cord. , 1981, The Journal of physiology.

[65]  R. Brownstone,et al.  Spinal cholinergic interneurons regulate the excitability of motoneurons during locomotion , 2007, Proceedings of the National Academy of Sciences.

[66]  Linying Wu,et al.  Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord. , 2005, Journal of neurophysiology.

[67]  J. Kellerth,et al.  Electron microscopic studies of serially sectioned cat spinal α‐motoneurons. II. A method for the description of architecture and synaptology of the cell body and proximal dendritic segments , 1979, The Journal of comparative neurology.

[68]  O. Kiehn.  Locomotor circuits in the mammalian spinal cord. , 2006, Annual review of neuroscience.

[69]  M. Tresch,et al.  Gap junctions and motor behavior , 2002, Trends in Neurosciences.

[70]  Y. Yanagawa,et al.  Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[71]  S. Cullheim,et al.  Postnatal changes in the termination pattern of recurrent axon collaterals of triceps surae alpha-motoneurons in the cat. , 1985, Brain research.

[72]  J R Wolpaw,et al.  Dorsal column but not lateral column transection prevents down-conditioning of H reflex in rats. , 1997, Journal of neurophysiology.

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

[74]  Thomas M. Jessell,et al.  A Hox Regulatory Network Establishes Motor Neuron Pool Identity and Target-Muscle Connectivity , 2005, Cell.

[75]  J. Schouenborg,et al.  Developmental Learning in a Pain-Related System: Evidence for a Cross-Modality Mechanism , 2003, The Journal of Neuroscience.

[76]  F. J. Alvarez,et al.  Calbindin D28k expression in immunohistochemically identified Renshaw cells. , 1998, Neuroreport.

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

[78]  P J Snow,et al.  The morphology of hair follicle afferent fibre collaterals in the spinal cord of the cat , 1977, The Journal of physiology.

[79]  David J. Anderson,et al.  Functionally Related Motor Neuron Pool and Muscle Sensory Afferent Subtypes Defined by Coordinate ETS Gene Expression , 1998, Cell.

[80]  L. Landmesser,et al.  The development of motor projection patterns in the chick hind limb. , 1978, The Journal of physiology.

[81]  F. J. Alvarez,et al.  The continuing case for the Renshaw cell , 2007, The Journal of physiology.

[82]  S. R. Wickramasinghe,et al.  A Hierarchical NGF Signaling Cascade Controls Ret-Dependent and Ret-Independent Events during Development of Nonpeptidergic DRG Neurons , 2007, Neuron.

[83]  Miklós Palkovits,et al.  Novel tracing paradigms—genetically engineered herpesviruses as tools for mapping functional circuits within the CNS: present status and future prospects , 2004, Progress in Neurobiology.

[84]  J. Schouenborg,et al.  Functional organization of the nociceptive withdrawal reflexes , 2004, Experimental Brain Research.

[85]  T. Jessell,et al.  The Homeodomain Factor Lbx1 Distinguishes Two Major Programs of Neuronal Differentiation in the Dorsal Spinal Cord , 2002, Neuron.

[86]  T. Jessell,et al.  Graded Activity of Transcription Factor Runx3 Specifies the Laminar Termination Pattern of Sensory Axons in the Developing Spinal Cord , 2006, Neuron.

[87]  T. Jessell,et al.  Conditional Rhythmicity of Ventral Spinal Interneurons Defined by Expression of the Hb9 Homeodomain Protein , 2005, The Journal of Neuroscience.

[88]  L. Landmesser,et al.  The distribution of motoneurones supplying chick hind limb muscles. , 1978, The Journal of physiology.

[89]  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.

[90]  J. Eccles,et al.  The convergence of monosynaptic excitatory afferents on to many different species of alpha motoneurones , 1957, The Journal of physiology.

[91]  J Schouenborg,et al.  Postnatal development of the nociceptive withdrawal reflexes in the rat: a behavioural and electromyographic study. , 1996, The Journal of physiology.

[92]  M. Hollyday.  Motoneuron histogenesis and the development of limb innervation. , 1980, Current topics in developmental biology.

[93]  H. Hultborn.  Spinal reflexes, mechanisms and concepts: From Eccles to Lundberg and beyond , 2006, Progress in Neurobiology.

[94]  V. Hamburger,et al.  An autoradiographic study of the formation of the lateral motor column in the chick embryo , 1977, Brain Research.

[95]  P. Wenner,et al.  Environmental Specification of Neuronal Connectivity , 1993, Neuron.

[96]  E. Frank,et al.  Muscle Spindle-Derived Neurotrophin 3 Regulates Synaptic Connectivity between Muscle Sensory and Motor Neurons , 2002, The Journal of Neuroscience.

[97]  A. G. Brown,et al.  Organization of the spinal cord , 1964 .

[98]  Keir G Pearson,et al.  Generating the walking gait: role of sensory feedback. , 2004, Progress in brain research.

[99]  S. Itohara,et al.  Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons , 2002, Nature Neuroscience.

[100]  E. Jankowska.  Interneuronal relay in spinal pathways from proprioceptors , 1992, Progress in Neurobiology.

[101]  A. G. Brown.  REVIEW ARTICLE THE DORSAL HORN OF THE SPINAL CORD , 1982 .

[102]  Silvia Arber,et al.  ETS Gene Er81 Controls the Formation of Functional Connections between Group Ia Sensory Afferents and Motor Neurons , 2000, Cell.

[103]  T. Jessell,et al.  Control of Interneuron Fate in the Developing Spinal Cord by the Progenitor Homeodomain Protein Dbx1 , 2001, Neuron.

[104]  Michael J. O'Donovan,et al.  Primary Afferent Synapses on Developing and Adult Renshaw Cells , 2006, The Journal of Neuroscience.

[105]  A. G. Brown,et al.  The morphology of group Ia afferent fibre collaterals in the spinal cord of the cat. , 1978, The Journal of physiology.

[106]  S. Arber,et al.  Control of neuronal phenotype: what targets tell the cell bodies , 2004, Trends in Neurosciences.

[107]  E. Frank,et al.  Prenatal Exposure to Elevated NT3 Disrupts Synaptic Selectivity in the Spinal Cord , 2007, The Journal of Neuroscience.

[108]  J. Munson,et al.  Retrograde effects on synaptic transmission at the Ia/motoneuron connection , 1999, Journal of Physiology-Paris.