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Parallel fiber plasticity

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Abstract

Cerebellar long-term depression (LTD) is classically observed when climbing fibers, originating from the inferior olive, and parallel fibers, axons of granule cells, are activated repetitively and synchronously. On the basis that the climbing fiber signals errors in motor performance, LTD provides a mechanism of learning whereby inappropriate motor signals, relayed to the cerebellar cortex by parallel fibers, are selectively weakened through their repeated, close temporal association with climbing fiber activity. LTD therefore provides a cellular substrate for error-driven motor learning in the cerebellar cortex. In recent years, it has become apparent that depression at this synapse can also occur without the need for concurrent climbing fiber activation provided the parallel fibers are activated in such a way as to mobilize calcium within the Purkinje cell. A form of long-term potentiation (LTP) has also been uncovered at this synapse, which similarly relies only upon parallel fiber activation. In brain slice preparations and contrary to expectation, each of these forms of parallel fiber induced plasticity, as well as classical LTD, does not remain confined to activated parallel fibers as previously thought, but both depression and potentiation have the capacity to spread to neighboring parallel fiber synapses several tens of microns away from the activated fibers. Here, the cellular mechanisms responsible for the induction and heterosynaptic spread of parallel fiber LTP and LTD are compared to those involved in classical LTD and the physiological implications that the heterosynaptic spread of plasticity may have on cerebellar signal processing are discussed.

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References

  1. Ito M., Sakurai M., Tongroach P. Climbing fiber induced depression of both mossy fiber responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J Physiol (Lond) 1982; 324: 113–134.

    CAS  Google Scholar 

  2. Karachot L., Kado RT., Ito M. Stimulus parameters for induction of long-term depression inin vitro rat Purkinje cells. Neurosci Res 1995; 21: 161–168.

    Article  Google Scholar 

  3. Chen C., Thompson RF. Temporal specificity of long-term depression in parallel fiber-Purkinje synapses in rat cerebellar slice. Learn Memory 1995; 2: 185–198.

    Article  CAS  Google Scholar 

  4. Schreurs BG., Oh M., Alkon DL. Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice. J Neurophysiol 1996; 753: 1051–1060.

    Google Scholar 

  5. Wang SS., Denk W., Hausser M. Coincidence detection in single dendritic spines mediated by calcium release. Nature Neuroscience 2000; 3: 1266–1273.

    Article  PubMed  CAS  Google Scholar 

  6. Ekerot CF., Kano M. Long-term depression of parallel fiber synapses following stimulation of climbing fibers. Brain Res 1985; 342: 357–360.

    Article  PubMed  CAS  Google Scholar 

  7. Kano M., Kato M. Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature 1987; 325: 276–279.

    Article  PubMed  CAS  Google Scholar 

  8. Marr D. A theory of cerebellar cortex. J Physiol (Lond) 1969; 202: 437–470.

    CAS  Google Scholar 

  9. Albus JS. A theory of cerebellar function. Math Biosci 1971; 28: 167–171.

    Google Scholar 

  10. Nunzi MG., Birnstiel S., Bhattacharyya BJ., Slater NT., Mugnaini E. Unipolar brush cells form a glutamatergic projection system within the mouse cerebellar cortex. J Comp Neurol 2001; 434: 329–341.

    Article  PubMed  CAS  Google Scholar 

  11. Gundappa-Sulur G., De Schutter E., Bower JM. Ascending granule cell axon: an important component of cerebellar cortical circuitry. J Comp Neurol 1999; 408: 580–596.

    Article  PubMed  CAS  Google Scholar 

  12. Napper RM., Harvey RJ. Number of parallel fiber synapses on an individual Purkinje cell in the cerebellum of the rat. J Comp Neurol 1988; 274: 168–177.

    Article  PubMed  CAS  Google Scholar 

  13. Mugnaini E. The length of cerebellar parallel fibers in chicken and rhesus monkey. J Comp Neurol 1983; 220: 7–15.

    Article  PubMed  CAS  Google Scholar 

  14. Larramendi EM., Victor T. Synapses on the Purkinje cell spines in the mouse. An electronmicroscopic study. Brain Res 1967; 5: 15–30.

    CAS  Google Scholar 

  15. Eccles JC., Llinas R., Sasaki K. The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum. J Physiol (Lond) 1966; 182: 268–296.

    CAS  Google Scholar 

  16. Thach WT. Somatosensory receptive fields of single units in cat cerebellar cortex. J Neurophysiol 1967; 30: 675–696.

    PubMed  Google Scholar 

  17. Voogd J., Glickstein M. The anatomy of the cerebellum. Trends Cog Sci 1998; 2: 307–313.

    Article  Google Scholar 

  18. Crepel F., Dhanjal SS., Sears TA. Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje-cell dendrites in the rat—anin vitro study. J Physiol (Lond) 1982; 329: 297–317.

    CAS  Google Scholar 

  19. Konnerth A., Llano I., Armstrong CM. Synaptic currents in cerebellar Purkinje cells. Proc Natl Acad Sci USA 1990; 87: 2662–2665.

    Article  PubMed  CAS  Google Scholar 

  20. Perkel DJ., Hestrin S., Sah P., Nicoll RA. Excitatory synaptic currents in Purkinje cells. Proc R Soc Lond B Biol Sci 1990; 241(1301): 116–121.

    Article  CAS  Google Scholar 

  21. Petralia RS., Zhao HM., Wang YX., Wenthold RJ. Variations in the tangential distribution of postsynaptic glutamate receptors in Purkinje cell parallel and climbing fiber synapses during development. Neuropharmacol 1998; 37(10-11): 1321–1334.

    Article  CAS  Google Scholar 

  22. Baude A., Molnar E., Latawiek D., Mcllhinney, Somogyi P. Synaptic and nonsynaptic localization of the glur1 subunit of the AMPA-type excitatory amino acid receptor in the rat cerebellum. J Neurosci 1994; 14: 2830–2843.

    PubMed  CAS  Google Scholar 

  23. Baude A., Nusser Z., Roberts JDB., Mulvihill E., McIlhinney RAJ., Somogyi P. The metabotropic glutamate receptor (mGluR1a) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 1993; 11: 771–787.

    Article  PubMed  CAS  Google Scholar 

  24. Nusser Z., Mulvihill E., Streit P., Somogyi P. Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization. Neurosci 1994; 61: 421–427.

    Article  CAS  Google Scholar 

  25. Batchelor AM., Madge DJ., Garthwaite J. Synaptic activation of metabotropic glutamate receptors in the parallel fibre-Purkinje cell pathway in rat cerebellar slices. Neurosci 1994; 63: 911–915.

    Article  CAS  Google Scholar 

  26. Batchelor AM., Garthwaite J. Frequency detection and temporally-dispersed synaptic signal association through a metabotropic glutamate receptor pathway. Nature 1997; 385: 74–77.

    Article  PubMed  CAS  Google Scholar 

  27. Tempia F., Miniaci MC., Anchisi D., Strata P. Postsynaptic current mediated by metabotropic glutamate receptors in cerebellar Purkinje cells. J Neurophysiol 1998; 80: 520–528.

    PubMed  CAS  Google Scholar 

  28. Knopfel T., Anchisi D., Alojado ME., Tempia F., Strata P. Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells. Eur J Neurosci 2000; 12: 2199–2204.

    Article  PubMed  CAS  Google Scholar 

  29. Staub C., Vranesic I., Knopfel T. Responses to metabotropic glutamate receptor activation in cerebellar Purkinje cells—induction of an inward current. Eur J Neurosci 1992; 4: 832–839.

    Article  PubMed  Google Scholar 

  30. Audinat E., Knopfel T., Gahwiler BH. Responses to excitatory amino acids of Purkinje cells’ and neurones of the deep nuclei in cerebellar slice cultures. J Physiol (Lond) 1990; 430: 297–313.

    CAS  Google Scholar 

  31. Ajima A., Hensch T., Kado RT., Ito M. Differential blocking action of JORO spider toxin analog on parallel fiber and climbing fiber synapses in cerebellar Purkinje cells. Neurosci 1991; 12: 281–286.

    Article  CAS  Google Scholar 

  32. Koike M., Iino M., Ozawa S. Blocking effect of 1-naphthyl acetyl spermine on Ca2+-permeable AMPA receptors in cultured rat hippocampal neurons. Neurosci Res 1997; 29: 27–36.

    Article  PubMed  CAS  Google Scholar 

  33. Blaschke M., Keller BU., Rivosecchi R., Hollmann M., Heinemann S., Konnerth A. A single amino acid determines the subunit-specific spider toxin block of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate /kainate receptor channels. Proc Natl Acad Sci USA 1993; 90: 6528–6532.

    Article  PubMed  CAS  Google Scholar 

  34. Kano M., Schneggenburger R., Verkhratsky A., Konnerth A. Depolarization-induced calcium signals in the somata of cerebellar Purkinje neurons. Neurosci Res 1995; 24: 87–95.

    Article  PubMed  CAS  Google Scholar 

  35. Ross WN., Werman R. Mapping calcium transients in the dendrites of Purkinje-cells from the guinea-pig cerebellumin vitro. J Physiol (Lond) 1987; 389: 319–336.

    CAS  Google Scholar 

  36. Miyakawa H., Lev-Ram V., Lasser-Ross N., Ross WN. Calcium transients evoked by climbing fiber and parallel fiber synaptic inputs in guinea pig cerebellar Purkinje neurons. J Neurophysiol 1992; 68: 1178–1189.

    PubMed  CAS  Google Scholar 

  37. Watanabe S., Takagi H., Miyasho T., Inoue M., Kirino Y., Kudo Y et al. Differential roles of two types of voltage-gated Ca2+ channels in he dendrites of rat cerebellar Purkinje neurons. Brain Res 1998; 791: 43–55.

    Article  PubMed  CAS  Google Scholar 

  38. Konnerth A., Dreessen J., Augustine GJ. Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells. Proc Natl Acad Sci USA 1992; 89: 7051–7055.

    Article  PubMed  CAS  Google Scholar 

  39. Sakurai M. Calcium is an intracellular mediator of the climbing fibre induction of cerebellar long-term depression. Proc Natl Acad Sci USA 1990; 87: 3383–3385.

    Article  PubMed  CAS  Google Scholar 

  40. Hemart N., Daniel H., Jaillard D., Crepel F. Receptors and second messengers involved in long-term depression in rat cerebellar slicesin vitro: a reappraisal. Eur J Neurosci 1995; 7: 45–53.

    Article  PubMed  CAS  Google Scholar 

  41. Linden DJ., Smeyne M., Connor JA. Induction of cerebellar longterm depression in culture requires postsynaptic action of sodium ions. Neuron 1993; 11: 1093–1110.

    Article  PubMed  CAS  Google Scholar 

  42. Aiba A., Kano M., Chen C., Stanton ME., Fox GD., Herrup K et al. Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell 1994; 79: 377–388.

    Article  PubMed  CAS  Google Scholar 

  43. Conquet F., Bashir ZI., Davies CH., Daniel H., Ferraguti F., Bordi F et al. Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature 1994; 372: 237–243.

    Article  PubMed  CAS  Google Scholar 

  44. Hartell NA. Induction of cerebellar long-term depression requires activation of glutamate metabotropic receptors. Neuro Report 1994; 5: 913–916.

    CAS  Google Scholar 

  45. Linden DJ., Dickenson MH., Smeyne M., Connor JA. A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron 1991; 7: 81–89.

    Article  PubMed  CAS  Google Scholar 

  46. Shigemoto R., Abe T., Nomura S., Nakanishi S., Hirano T. Antibodies inactivating mgGluR1 metabotropic glutamate receptor block long-term depression in cultured Purkinje cells. Neuron 1994; 12: 1245–1255.

    Article  PubMed  CAS  Google Scholar 

  47. Ichise T., Kano M., Hashimoto K., Yanagihara D., Nakao K., Shigemoto R et al. mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination. Science 2000; 288(5472): 1832–1835.

    Article  PubMed  CAS  Google Scholar 

  48. Sugimori M., Llinas RR. Real-time imaging of calcium influx in mammalian cerebellar Purkinje cellsin vitro. Proc Natl Acad Sci USA 1990; 87: 5084–5088.

    Article  PubMed  CAS  Google Scholar 

  49. Batchelor AM., Madge DJ., Garthwaite J. Synaptic activation of metabotropic glutamate receptors in the parallel fibre-Purkinje cell pathway in rat cerebellar slices. Neurosci 1994; 63: 911–915.

    Article  CAS  Google Scholar 

  50. Ito M., Karachot L. Protein kinases and phosphatase inhibitors mediating long-term desensitization of glutamate receptors in cerebellar Purkinje cells. Neurosci 1992; 14: 27–38.

    Article  CAS  Google Scholar 

  51. Crepel F., Krupa M. Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. Anin vitro study. Brain Res 1988; 458: 397–401.

    CAS  Google Scholar 

  52. Hartell NA. cGMP acts within cerebellar Purkinje cells to produce long term depression via mechanisms involving PKC and PKG. NeuroReport 1994; 5: 833–836.

    Article  PubMed  CAS  Google Scholar 

  53. Linden DJ. Input-specific induction of cerebellar long-term depression does not require presynaptic alteration. Learn Memory 1994; 1: 121–128.

    CAS  Google Scholar 

  54. Linden DJ., Connor JA. Participation of postsynaptic PKC in cerebellar long-term depression in culture. Science 1991; 254: 1656–1659.

    Article  PubMed  CAS  Google Scholar 

  55. Hartell NA. Inhibition of cGMP breakdown promotes the induction of cerebellar long-term depression. J Neurosci 1996; 16: 2881–2890.

    PubMed  CAS  Google Scholar 

  56. DeZeeuw CI., Hansel C., Bian F., Koekkoek SE., VanAlphen AM., Linden DJ et al. Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. Neuron 1998; 20: 495–508.

    Article  CAS  Google Scholar 

  57. Boxall AR., Lancaster B., Garthwaite J. Tyrosine kinase is required for long-term depression in the cerebellum. Neuron 1996; 16: 805–813.

    Article  PubMed  CAS  Google Scholar 

  58. Linden DJ. Phospholipase A2 controls the induction of shortterm versus long-term depression in the cerebellar Purkinje neuron in culture. Neuron 1995; 15: 1393–1401.

    Article  PubMed  CAS  Google Scholar 

  59. Reynolds T., Hartell NA. Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD. Neuro Report 2001; 12: 133–136.

    CAS  Google Scholar 

  60. Kasono K., Hirano T. Involvement of inositol trisphosphate in cerebellar long-term depression. NeuroReport 1995; 6: 569–572.

    Article  PubMed  CAS  Google Scholar 

  61. Finch EA., Augustine GJ. Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature 1998; 396: 753–756.

    Article  PubMed  CAS  Google Scholar 

  62. Takechi H., Eilers J., Konnerth A. A new class of synaptic response involving calcium release in dendritic spines. Nature 1998; 396: 757–760.

    Article  PubMed  CAS  Google Scholar 

  63. Inoue T., Kato K., Kohda K., Mikoshiba K. Type 1 inositol 1,4,5-trisphosphate receptor is required for induction of long-term depression in cerebellar Purkinje neurons. J Neurosci 1998; 18: 5366–5373.

    PubMed  CAS  Google Scholar 

  64. Miyata M., Finch EA., Khiroug L., Hashimoto K., Hayasaka S., Oda SI et al. Local calcium release in dendritic spines required for long-term synaptic depression. Neuron 2000; 28: 233–244.

    Article  PubMed  CAS  Google Scholar 

  65. Miyata M., Kim HT., Hashimoto K., Lee TK., Cho SY., Jiang H et al. Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice. Eur J Neurosci 2001; 13: 1945–1954.

    Article  PubMed  CAS  Google Scholar 

  66. Umemori H., Inoue T., Kume S., Sekiyama N., Nagao M., Itoh H et al. Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha subunit. Science 1997; 276: 1878–1881.

    Article  PubMed  CAS  Google Scholar 

  67. Jayaraman T., Ondrias K., Ondriasova E., Marks AR. Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation. Science 1996; 272: 1492–1494.

    Article  PubMed  CAS  Google Scholar 

  68. Oancea E., Meyer T. Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals. Cell 1998; 95: 307–318.

    Article  PubMed  CAS  Google Scholar 

  69. Nakanishi S. Metabotropic glutamate receptors-synaptic transmission, modulation, and plasticity. Neuron 1994; 13: 1031–1037.

    Article  PubMed  CAS  Google Scholar 

  70. Hemart N., Daniel H., Jaillard D., Crepel F. Properties of glutamate receptors are modified during long-term depression in rat cerebellar Purkinje cells. Neurosci 1994; 19: 213–221.

    Article  CAS  Google Scholar 

  71. Matsuda S., Launey T., Mikawa S., Hirai H. Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons. EMBO J 2000; 19: 2765–2774.

    Article  PubMed  CAS  Google Scholar 

  72. Wang YT., Linden DJ. Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 2000; 25: 635–647.

    Article  PubMed  CAS  Google Scholar 

  73. Miyata M., Okada D., Hashimoto K., Kano M., Ito M. Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression. Neuron 1999; 22: 763–775.

    Article  PubMed  CAS  Google Scholar 

  74. Araki K., Meguro H., Kushiya E., Takayama C., Inoue Y., Mishina M. Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar Purkinje cells. Biochem Biophys Res Commun 1993; 197: 1267–1276.

    Article  PubMed  CAS  Google Scholar 

  75. Lomeli H., Sprengel R., Laurie DJ., Kohr G., Herb A., Seeburg PH et al. The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett 1993; 315: 318–322.

    Article  PubMed  CAS  Google Scholar 

  76. Kashiwabuchi N., Ikeda K., Araki K., Hirano T., Shibuki K., Katsuwada T et al. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in Glurd2 mutant mice. Cell 1995; 81: 245–252.

    Article  PubMed  CAS  Google Scholar 

  77. Kurihara H., Hashimoto K., Kano M., Takayama C., Sakimura K., Mishina M et al. Impaired parallel fiber Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta 2 subunit. J Neurosci 1997; 17: 9613–9623.

    PubMed  CAS  Google Scholar 

  78. Zuo J., DeJager PL., Takahashi KA., Jiang WN., Linden DJ., Heintz N. Neurodegeneration in Lurcher mice caused by mutation in delta 2 glutamate receptor gene. Nature 1997; 388: 769–773.

    Article  PubMed  CAS  Google Scholar 

  79. Reynolds T., Hartell NA. An evaluation of the synapse-specificity of long-term depression induced in rat cerebellar slices. J Physiol (Lond) 2000; 527: 563–577.

    Article  CAS  Google Scholar 

  80. Aramori I., Nakanishi S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 1992; 8: 757–765.

    Article  PubMed  CAS  Google Scholar 

  81. Dumuis A., Sebben M., Fagni L., Prezeau L., Manzoni O., Cragoe EJ et al. Stimulation by glutamate receptors of arachidonic-acid release depends on the Na+/Ca2+ exchanger in neuronal cells. Mol Pharmacol 1993; 43: 976–981.

    PubMed  CAS  Google Scholar 

  82. Lombardi G., Leonardi P., Moroni F. Metabotropic glutamate receptors, transmitter output and fatty acids: studies in rat brain slices. Br J Pharmacol 1996; 117: 189–195.

    PubMed  CAS  Google Scholar 

  83. Lin LL., Wartmann M., Lin AY., Knopf JL., Seth A., Davis RJ. PLA2 is phosphorylated and activated by MAP kinase. Cell 1993; 72: 269–278.

    Article  PubMed  CAS  Google Scholar 

  84. Bredt DS., Glatt DE., Hwang PM., Fotuhi M., Dawson TM., Snyder SH. Nitric oxide synthase protein and mRNA are discretely located in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 1991; 7: 615–624.

    Article  PubMed  CAS  Google Scholar 

  85. Southam E., Morris R., Garthwaite J. Sources and targets of nitric oxide in rat cerebellum. Neurosci 1992; 137: 241–244.

    CAS  Google Scholar 

  86. Ariano MA., Lewicki JA., Brandwein HJ., Murad F. Immunohistochemical localization of guanylate cyclase within neurons of rat brain. Proc Natl Acad Sci USA 1982; 79: 1316–1320.

    Article  PubMed  CAS  Google Scholar 

  87. Detre JA., Nairn AC., Aswad DW., Greengard P. Localization in mammalian brain of G-substrate, a specific substrate for guanosine 3’,5’-cyclic monophosphate-dependent protein kinase. J Neurosci 1984; 4: 2843–2849.

    PubMed  CAS  Google Scholar 

  88. Schlichter DJ., Detre JA., Aswad DW., Chehrazi B., Greengard P. Localization of cyclic GMP-dependent protein kinase and substrate in mammalian cerebellum. Proc Natl Acad Sci USA 1980; 77: 5537–5541.

    Article  PubMed  CAS  Google Scholar 

  89. Lohmann SM., Walter U., Miller PE., Greengard P., Camilli P. Immunohistochemical localization of cyclic-GMP-dependent protein kinase in the mammalian brain. Proc Natl Acad Sci USA 1981; 78: 653–657.

    Article  PubMed  CAS  Google Scholar 

  90. Daniel H., Hemart N., Jaillard D., Crepel F. Long-term depression requires nitric oxide and guanosine 3’ 5’cyclic monophosphate production in rat cerebellar Purkinje cells. Eur J Neurosci 1993; 5: 1079–1082.

    Article  PubMed  CAS  Google Scholar 

  91. Shibuki K., Okada D. Roles of nitric oxide in cerebellar synaptic plasticity. In: Kawai N, editor. Neuroreceptors, ion channels and the brain. Elsevier Science, 1992: 161–169.

  92. Crepel F., Jaillard D. Protein kinases, nitric oxide and long-term depression of synapses in the cerebellum. Neuro Report 1990; 1: 133–136.

    CAS  Google Scholar 

  93. Kotera J., Yanaka N., Fujishige K., Imai Y., Akatsuka H., Ishizuka T et al. Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development. Eur J Biochem 1997; 249: 434–442.

    Article  PubMed  CAS  Google Scholar 

  94. Lev Ram V., Jiang T., Wood J., Lawrence DS., Tsien R. Synergies and coincidence requirements between NO, cGMP, and Ca2+ in the induction of cerebellar long-term depression. Neuron 1997; 18: 1025–1038.

    Article  Google Scholar 

  95. Lev Ram V., Makings LR., Keitz PF., Kao JY., Tsien RY. Longterm depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+transients. Neuron 1995; 15: 407–415.

    Article  Google Scholar 

  96. Hartell NA. Strong activation of parallel fibers produces localized calcium transients and a form of LTD that spreads to distant synapses. Neuron 1996; 16: 601–610.

    Article  PubMed  CAS  Google Scholar 

  97. Hartell NA. The intracellular mechanisms underlying parallel fiber-induced, heterosynaptic long-term depression in the cerebellum. Br J Pharmacol 1996; 119: 68.

    Google Scholar 

  98. Hartell NA. Two separate pathways for cerebellar LTD: NO-dependent and NO- independent. Behavior Brain Sci 1996; 19: 453.

    Google Scholar 

  99. Boxall AR., Garthwaite J. Long-term depression in rat cerebellum requires both NO synthase and NO-sensitive guanylyl cyclase. Eur J Neurosci 1996; 8: 2209–2212.

    Article  PubMed  CAS  Google Scholar 

  100. Glaum SR., Slater NT., Rossi DJ., MIller RJ. Role of metabotropic glutamate (t-ACPD) receptors at the parallel fiber-Purkinje cell synapse. J Neurophysiol 1992; 64: 1453–1462.

    Google Scholar 

  101. Linden DJ., Dawson TM., Dawson VL. An evaluation of the nitric oxide/cGMP-dependent protein kinase cascade in the induction of cerebellar long-term depression in culture. J Neurosci 1995; 15: 5098–5105.

    PubMed  CAS  Google Scholar 

  102. Shibuki K., Okada D. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature 1991; 349: 326–328.

    Article  PubMed  CAS  Google Scholar 

  103. Hartell NA. Receptors, second messengers and protein kinases required for heterosynaptic cerebellar long-term depression. Neuropharmacol 2000; 40: 148–161.

    Article  Google Scholar 

  104. Shibuki K., Kimura S. Dynamic properties of nitric oxide release from parallel fibres in rat cerebellar slices. J Physiol (Lond) 1997; 498: 443–452.

    CAS  Google Scholar 

  105. DeVente J., Bol JGJM., Berkelmans HS., Schipper J., Steinbusch HMW. Immunocytochemistry of cGMP in the cerebellum of the immature, adult, and aged rat; the involvement of nitric oxide. A micropharmacological study. Eur J Neurosci 1990; 2: 845–862.

    Article  Google Scholar 

  106. Shibuki K., Gomi H., Chen L., Bao SW., Kim JK., Wakatsuki H et al. Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in gfap mutant mice. Neuron 1996; 16: 587–599.

    Article  PubMed  CAS  Google Scholar 

  107. Hartell NA., Okada D. Imaging cGMP in cerebellar Purkinje cells. J Physiol (Lond) 1998; 509: 60P.

    Google Scholar 

  108. Hartell NA., Furuya S., Jacoby S., Okada D. Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells. NeuroReport 2001; 12: 25–28.

    Article  PubMed  CAS  Google Scholar 

  109. Honda A., Adams SR., Sawyer CL., Lev-Ram V., Tsien RY., Dostmann WR. Spatiotemporal dynamics of guanosine 3’,5’ cyclic monophosphate revealed by a genetically encoded, fluorescent indicator. Proc Natl Acad Sci USA 2001; 98: 2437–2442.

    Article  PubMed  CAS  Google Scholar 

  110. Wood J., Garthwaite J. Models of the diffusional spread of nitricoxide—implications for neural nitric-oxide signaling and its pharmacological properties. Neuropharmacol 1994; 33: 1235–1244.

    Article  CAS  Google Scholar 

  111. Midtgaard J., Lasser-Ross N., Ross WN. Spatial distribution of Ca2+ influx in turtle Purkinje cell dendrites in vitro: role of a transient outward current. J Neurophysiol 1993; 70: 2455–2469.

    PubMed  CAS  Google Scholar 

  112. Eilers J., Augustine GJ., Konnerth A. Subthreshold synaptic Ca2+signalling in fine dendrites and spines of cerebellar Purkinje neurons. Nature 1995; 373: 155–158.

    Article  PubMed  CAS  Google Scholar 

  113. Denk W., Sugimori M., Llinas R. Two types of calcium response limited to single spines in cerebellar Purkinje cells. Proc Natl Acad Sci USA 1995; 92: 8279–8282.

    Article  PubMed  CAS  Google Scholar 

  114. Eilers J., Takechi H., Finch EA., Augustine GJ., Konnerth A. Local dendritic Ca2+ signaling induces cerebellar long-term depression. Learn Memory 1997; 4: 159–168.

    Article  CAS  Google Scholar 

  115. Ekerot CF., Kano M. Stimulation parameters influencing climbing fiber induced long-term depression of parallel fiber synapses. Neurosci Res 1989; 6: 264–268.

    Article  PubMed  CAS  Google Scholar 

  116. Endo S., Suzuki M., Sumi M., Nairn AC., Morita R., Yamakawa K et al. Molecular identification of human G-substrate, a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells. Proc Natl Acad Sci USA 1999; 96: 2467–2472.

    Article  PubMed  CAS  Google Scholar 

  117. Wang SS., Khiroug L., Augustine GJ. Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. Proc Natl Acad Sci USA 2000; 97: 8635–8640.

    Article  PubMed  CAS  Google Scholar 

  118. Sakurai M. Synaptic modification of parallel fibre-Purkinje cell transmission inin vitro guinea-pig cerebellar slices. J Physiol (Lond) 1987; 394: 463–480.

    CAS  Google Scholar 

  119. Hirano T. Depression and potentiation of the synaptic transmission between a granule cell and a Purkinje cell in rat cerebellar culture. Neurosci Lett 1990; 119: 141–144.

    Article  PubMed  CAS  Google Scholar 

  120. Crepel F., Jaillard D. Pairing of pre-and postsynaptic responses in cerebellar Purkinje cells induces long-term changes in synaptic efficacyin vitro. J Physiol (Lond) 1991; 432: 123–141.

    CAS  Google Scholar 

  121. Shibuki K., Okada D. Cerebellar long-term potentiation under supressed postsynaptic Ca2+ activity. NeuroReport 1992; 3: 231–234.

    Article  PubMed  CAS  Google Scholar 

  122. Salin PA., Malenka RC., Nicoll RA. Cyclic-AMP mediates a presynaptic form of LTP at cerebellar parallel fiber synapses. Neuron 1996; 16: 797–803.

    Article  PubMed  CAS  Google Scholar 

  123. Linden DJ. Long-term potentiation of glial synaptic currents in cerebellar culture. Neuron 1997; 18: 983–994.

    Article  PubMed  CAS  Google Scholar 

  124. Nicoll RA., Malenka RC. Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 1995; 377(6545): 115–118.

    Article  PubMed  CAS  Google Scholar 

  125. Kimura S., Uchiyama S., Takahashi HE., Shibuki K. cAMPdependent long-term potentiation of nitric oxide release from cerebellar parallel fibers in rats. J Neurosci 1998; 18: 8551–8558.

    PubMed  CAS  Google Scholar 

  126. Meffert MK., Premack BA., Schulman H. Nitric oxide stimulates Ca2+-independent synaptic vesicle release. Neuron 1994; 12: 1235–1244.

    Article  PubMed  CAS  Google Scholar 

  127. Meffert MK., Calakos NC., Scheller RH., Schulman H. Nitric oxide modulates synaptic vesicle docking fusion reactions. Neuron 1996; 16: 1229–1236.

    Article  PubMed  CAS  Google Scholar 

  128. Haley JE., Wilcox GL., Chapman PF. The role of nitric oxide in hippocampal long-term potentiation. Neuron 1992; 8: 211–216.

    Article  PubMed  CAS  Google Scholar 

  129. Arancio O., Kiebler M., Lee CJ., LevRam V., Tsien RY., Kandel ER et al. Nitric-oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampalneurons. Cell 1996; 87: 1025–1035.

    Article  PubMed  CAS  Google Scholar 

  130. Son H., Hawkins RD., Martin K., Kiebler M., Huang PL., Fishman MC et al. Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell 1996; 87: 1015–1023.

    Article  PubMed  CAS  Google Scholar 

  131. Schuman EM., Madison DV. Locally distributed synaptic potentiation in the hippocampus. Science 1994; 263: 532–536.

    Article  PubMed  CAS  Google Scholar 

  132. Schuman EM., Madison DV. Nitric oxide and synaptic function. Annu Rev Neurosci 1994; 17: 153–183.

    Article  PubMed  CAS  Google Scholar 

  133. Jacoby S., Sims RE., Hartell NA. Nitric oxide is required for the induction and heterosynaptic spread of cerebellar LTP. J Physiol (Lond) 2001; 535: 825–839.

    Article  CAS  Google Scholar 

  134. Storm DR., Hansel C., Hacker B., Parent A., Linden DJ. Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant mice. Neuron 1998; 20: 1199–1210.

    Article  PubMed  CAS  Google Scholar 

  135. Petralia RS., Wang YX., Wenthold RJ. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci 1994; 14: 6102–6120.

    PubMed  CAS  Google Scholar 

  136. Casado M., Dieudonne S., Ascher P. Presynaptic N-methyl-D-aspartate receptors at the parallel fiber-Purkinje cell synapse. Proc Natl Acad Sci USA 2000; 97: 11593–11597.

    Article  PubMed  CAS  Google Scholar 

  137. Chen CF., Regehr WG. The mechanism of cAMP-mediated enhancement at a cerebellar synapse. J Neurosci 1997; 17: 8687–8694.

    PubMed  CAS  Google Scholar 

  138. Bredt DS., Ferris CD., Snyder SH. Nitric-oxide synthase regulatory sites—phosphorylation by cyclic amp-dependent proteinkinase, protein-kinase-c, and calcium calmodulin protein—kinase—identification of flavin and calmodulin bindingsites. J Biol Chem 1992; 267: 10976–10981.

    PubMed  CAS  Google Scholar 

  139. Okada D. Protein kinase C modulates calcium sensitivity of nitric oxide synthase in cerebellar slices. J Neurochem 1995; 64: 1298–1304.

    PubMed  CAS  Google Scholar 

  140. Inada H., Shindo H., Tawata M., Onaya T. cAMP regulates nitric oxide production and ouabain sensitive Na+, K+-ATPase activity in SH-SY5Y human neuroblastoma cells. Diabetologia 1998; 41: 1451–1458.

    Article  PubMed  CAS  Google Scholar 

  141. Inada H., Shindo H., Tawata M., Onaya T. Cilostazol, a cyclic AMP phosphodiesterase inhibitor, stimulates nitric oxide production and sodium potassium adenosine triphosphatase activity in SH-SY5Y human neuroblastoma cells. Life Sci 1999; 65: 1413–1422.

    Article  PubMed  CAS  Google Scholar 

  142. Brune B., Lapetina EG. Phosphorylation of nitric oxide synthase by protein kinase A. Biochem Biophys Res Comm 1991; 181: 921–926.

    Article  PubMed  CAS  Google Scholar 

  143. Polte T., Schroder H. Cyclic AMP mediates endothelial protection by nitric oxide. Biochem Biophys Res Comm 1998; 251: 460–465.

    Article  PubMed  CAS  Google Scholar 

  144. Dubey RK., Gillespie DG., Jackson EK. Cyclic AMP-adenosine pathway induces nitric oxide synthesis in aortic smooth muscle cells. Hypertension 1998; 31(1 Pt 2): 296–302.

    PubMed  CAS  Google Scholar 

  145. Barbour B. Synaptic currents evoked in Purkinje cells by stimulating individual granule cells. Neuron 1993; 11: 759–769.

    Article  PubMed  CAS  Google Scholar 

  146. Merrill EG., Wall PD., Yaksh TL. Properties of two unmyelinated fibre tracts of the central nervous system: lateral Lissauer tract, and parallel fibres of the cerebellum. J Physiol (Lond) 1978; 284: 127–145.

    CAS  Google Scholar 

  147. DeSchutter E. Cerebellar long-term depression might normalize excitation of Purkinje cells, a hypothesis. Trends Neurosci 1995; 18: 291–295.

    Article  CAS  Google Scholar 

  148. Montgomery JC., Bodznick D. An adaptive filter that cancels selfinduced noise in the electrosensory and lateral line mechanosensory systems of fish. Neurosci Lett 1994; 174: 145–148.

    Article  PubMed  CAS  Google Scholar 

  149. Bell CC., Han VZ., Sugawara Y., Grant K. Synaptic plasticity in a cerebellum-like structure depends on temporal order. Nature 1997; 387: 278–281.

    Article  PubMed  CAS  Google Scholar 

  150. Schreurs BG., Alkon DL. Rabbit cerebellar slice analysis of longterm depression and its role in classical conditioning. Brain Res 1993; 631: 235–240.

    Article  PubMed  CAS  Google Scholar 

  151. Hausser M., Clark BA. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 1997; 19: 665–678.

    Article  PubMed  CAS  Google Scholar 

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Hartell, N.A. Parallel fiber plasticity. Cerebellum 1, 3–18 (2002). https://doi.org/10.1080/147342202753203041

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