Axonal Motility and Its Modulation by Activity Are Branch-Type Specific in the Intact Adult Cerebellum

We performed two-photon in vivo imaging of cerebellar climbing fibers (CFs; the terminal arbor of olivocerebellar axons) in adult mice. CF ascending branches innervate Purkinje cells while CF transverse branches show a near complete failure to form conventional synapses. Time-lapse imaging over hours or days revealed that ascending branches were very stable. However, transverse branches were highly dynamic, exhibiting rapid elongation and retraction and varicosity turnover. Thus, different branches of the same axon, with different innervation patterns, display branch type-specific motility in the adult cerebellum. Furthermore, dynamic changes in transverse branch length were almost completely suppressed by pharmacological stimulation of olivary firing.

[1]  Mihaly Kollo,et al.  Novel Subcellular Distribution Pattern of A-Type K+ Channels on Neuronal Surface , 2006, The Journal of Neuroscience.

[2]  B. Giros,et al.  A Third Vesicular Glutamate Transporter Expressed by Cholinergic and Serotoninergic Neurons , 2002, The Journal of Neuroscience.

[3]  G. Shepherd,et al.  Transient and Persistent Dendritic Spines in the Neocortex In Vivo , 2005, Neuron.

[4]  D. Perrais,et al.  Fast Regulation of Axonal Growth Cone Motility by Electrical Activity , 2007, The Journal of Neuroscience.

[5]  D. Harriman.  CEREBELLAR CORTEX, CYTOLOGY AND ORGANIZATION , 1974 .

[6]  D. Attwell,et al.  Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake , 1990, Nature.

[7]  J. R. Newton,et al.  Remodeling of Synaptic Structure in Sensory Cortical Areas In Vivo , 2006, The Journal of Neuroscience.

[8]  A. Scheibel,et al.  Observations on the intracortical relations of the climbing fibers of the cerebellum. A Golgi study , 1954, The Journal of comparative neurology.

[9]  A. G. Roseberry,et al.  Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin , 2004, Science.

[10]  Masao Ito.  The Cerebellum And Neural Control , 1984 .

[11]  D. Linden,et al.  Differential Maturation of Climbing Fiber Innervation in Cerebellar Vermis , 2004, The Journal of Neuroscience.

[12]  Martin P Meyer,et al.  Evidence from In Vivo Imaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms , 2006, The Journal of Neuroscience.

[13]  C. Jahr,et al.  Ectopic Release of Synaptic Vesicles , 2003, Neuron.

[14]  J. Storm-Mathisen,et al.  The Expression of Vesicular Glutamate Transporters Defines Two Classes of Excitatory Synapse , 2001, Neuron.

[15]  C. Gilbert,et al.  Axonal sprouting accompanies functional reorganization in adult cat striate cortex , 1994, Nature.

[16]  Michael Unser,et al.  A pyramid approach to subpixel registration based on intensity , 1998, IEEE Trans. Image Process..

[17]  G. Knott,et al.  Formation of Dendritic Spines with GABAergic Synapses Induced by Whisker Stimulation in Adult Mice , 2002, Neuron.

[18]  Nicholas C. Spitzer,et al.  Electrical activity in early neuronal development , 2006, Nature.

[19]  P. Strata,et al.  Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses , 1991, The Journal of comparative neurology.

[20]  R. Llinás,et al.  Serotonin Modulation of Inferior Olivary Oscillations and Synchronicity: A Multiple‐electrode Study in the Rat Cerebellum , 1995, The European journal of neuroscience.

[21]  K. Fujita.  [Two-photon laser scanning fluorescence microscopy]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[22]  Y Shinoda,et al.  Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat , 1999, The Journal of comparative neurology.

[23]  H. Jörntell,et al.  Ketamine and xylazine depress sensory-evoked parallel fiber and climbing fiber responses. , 2007, Journal of neurophysiology.

[24]  G. Feng,et al.  Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex , 2005, PLoS biology.

[25]  Wade G Regehr,et al.  Monitoring Presynaptic Calcium Dynamics in Projection Fibers by In Vivo Loading of a Novel Calcium Indicator , 2000, Neuron.

[26]  R. Fremeau,et al.  Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. , 2000, Science.

[27]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[28]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[29]  B. Hyman,et al.  Adeno-associated virus vectors serotyped with AAV8 capsid are more efficient than AAV-1 or -2 serotypes for widespread gene delivery to the neonatal mouse brain , 2006, Neuroscience.

[30]  K. Svoboda,et al.  Cell Type-Specific Structural Plasticity of Axonal Branches and Boutons in the Adult Neocortex , 2006, Neuron.

[31]  Yi Zuo,et al.  Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex , 2005, Nature.

[32]  J. Szentágothai,et al.  Identification under the electron microscope of climbing fibers and their synaptic contacts , 2004, Experimental Brain Research.

[33]  M. Schäfer,et al.  Molecular Cloning and Functional Identification of Mouse Vesicular Glutamate Transporter 3 and Its Expression in Subsets of Novel Excitatory Neurons* , 2002, The Journal of Biological Chemistry.

[34]  C. Jahr,et al.  High-Concentration Rapid Transients of Glutamate Mediate Neural-Glial Communication via Ectopic Release , 2005, The Journal of Neuroscience.

[35]  D. Copenhagen,et al.  The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Rafael Yuste,et al.  Bidirectional Regulation of Hippocampal Mossy Fiber Filopodial Motility by Kainate Receptors A Two-Step Model of Synaptogenesis , 2003, Neuron.

[37]  V. Kilman,et al.  Induction of Multiple Synapses by Experience in the Visual Cortex of Adult Rats , 1997, Neurobiology of Learning and Memory.

[38]  Jianli Li,et al.  Stabilization of Axon Branch Dynamics by Synaptic Maturation , 2006, The Journal of Neuroscience.

[39]  C. D. De Zeeuw,et al.  Inferior olivary‐induced expression of Fos‐like immunoreactivity in the cerebellar nuclei of wild‐type and Lurcher mice , 1999, The European journal of neuroscience.

[40]  P. Somogyi,et al.  Climbing Fiber Innervation of NG2-Expressing Glia in the Mammalian Cerebellum , 2005, Neuron.

[41]  Hee-Sup Shin,et al.  P/Q-type Ca2+ channel alpha1A regulates synaptic competition on developing cerebellar Purkinje cells. , 2004, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  Karel Svoboda,et al.  Experience-dependent and cell-type-specific spine growth in the neocortex , 2006, Nature.

[43]  C. Gilbert,et al.  Axons and Synaptic Boutons Are Highly Dynamic in Adult Visual Cortex , 2006, Neuron.

[44]  Joan F. Lorden,et al.  Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the awake genetically dystonic rat , 2002, Experimental Brain Research.

[45]  V. Popov,et al.  Hibernation-induced structural changes in synaptic contacts between mossy fibres and hippocampal pyramidal neurons , 1992, Neuroscience.

[46]  E Gould,et al.  Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  C. Compoint,et al.  Harmaline induced tremor III. A combined simple units, horseradish peroxidase, and 2-deoxyglucose study of the olivocerebellar system in the rat , 2004, Experimental Brain Research.

[48]  S. Palay,et al.  Cerebellar Cortex: Cytology and Organization , 1974 .

[49]  N. Kasthuri,et al.  Long-term dendritic spine stability in the adult cortex , 2002, Nature.

[50]  W. Gan,et al.  Development of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex , 2005, Neuron.

[51]  R. Llinás,et al.  The olivo-cerebellar system: Functional properties as revealed by harmaline-induced tremor , 1973, Experimental Brain Research.

[52]  W. Gan,et al.  Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex , 2007, Nature Neuroscience.

[53]  A. Bragin,et al.  Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation , 1992, Neuroscience.

[54]  E. Dent,et al.  Cytoskeletal Dynamics and Transport in Growth Cone Motility and Axon Guidance , 2003, Neuron.

[55]  Masahiko Watanabe,et al.  Distal Extension of Climbing Fiber Territory and Multiple Innervation Caused by Aberrant Wiring to Adjacent Spiny Branchlets in Cerebellar Purkinje Cells Lacking Glutamate Receptor δ2 , 2002, The Journal of Neuroscience.

[56]  Christian Rosenmund,et al.  Identification of Differentiation-Associated Brain-Specific Phosphate Transporter as a Second Vesicular Glutamate Transporter (VGLUT2) , 2001, The Journal of Neuroscience.

[57]  J. Goodhouse,et al.  Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice , 2000, Nature Neuroscience.

[58]  J. Bower,et al.  Multiple Purkinje Cell Recording in Rodent Cerebellar Cortex , 1989, The European journal of neuroscience.