Skip to main content
Log in

Is Purkinje Neuron Hyperpolarisation Important for Cerebellar Synaptic Plasticity? A Retrospective and Prospective Analysis

  • Review
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Two recent studies have demonstrated that the dendritic Ca2+ signal associated with a climbing fibre (CF) input to the cerebellar Purkinje neuron (PN) depends on the membrane potential (Vm). Specifically, when the cell is hyperpolarised, this signal is mediated by T-type voltage-gated Ca2+ channels; in contrast, when the cell is firing, the CF-PN signal is mediated by P/Q-type voltage-gated Ca2+ channels. When the CF input is paired with parallel fibre (PF) activity, the signal is locally amplified at the sites of PF-activated synapses according to the Vm at the time of the CF input, suggesting that the standing Vm is a critical parameter for the induction of PF synaptic plasticity. In this review, I analyse how the Vm can potentially play a role in cerebellar learning focussing, in particular, on the hyperpolarised state that appears to occur episodically, since PNs are mostly firing under physiological conditions. By revisiting the recent literature reporting in vivo recordings and synaptic plasticity studies, I speculate on how a putative role of the PN Vm can provide an interpretation for the results of these studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Eccles JC, Ito M, Szentagotai J. The cerebellum as a neuronal machine. Berlin, Heidelberg, New York: Springer Verlag; 1967.

    Book  Google Scholar 

  2. Jelitai M, Puggioni P, Ishikawa T, Rinaldi A, Duguid I. Dendritic excitation-inhibition balance shapes cerebellar output during motor behaviour. Nat Commun. 2016;7:13722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Marr D. A theory of cerebellar cortex. J Physiol. 1969;202:437–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Albus JS. A theory of cerebellar function. Math Biosci. 1971;28:167–71.

    Google Scholar 

  5. Ito M, Sakurai M, Tongroach P. Climbing fiber induced depression of both mossy fiber responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J Physiol. 1982;324:113–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Suvrathan A, Raymond JL. Depressed by learning-heterogeneity of the plasticity rules at parallel fiber synapses onto Purkinje cells. Cerebellum. 2018;17:747–55.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jörntell H, Hansel C. Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fiber–Purkinje cell synapses. Neuron. 2006;52:227–38.

    Article  PubMed  CAS  Google Scholar 

  8. Vogt KE, Canepari M. On the induction of postsynaptic granule cell-Purkinje neuron LTP and LTD. Cerebellum. 2010;9:284–90.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wang SS, Denk W, Hausser M. Coincidence detection in single dendritic spines mediated by calcium release. Nat Neurosci. 2000;3:1266–73.

    Article  CAS  PubMed  Google Scholar 

  10. Brenowitz SD, Regehr WG. Associative short-term synaptic plasticity mediated by endocannabinoids. Neuron. 2005;45:419–31.

    Article  CAS  PubMed  Google Scholar 

  11. Ait Ouares K, Canepari M. The origin of physiological local mGluR1 supralinear Ca2+ signals in cerebellar Purkinje neurons. J Neurosci. 2020;40:1795–809.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Napper RM, Harvey RJ. Number of parallel fibre synapses on an individual Purkinje cell in the cerebellum of the rat. J Comp Neurol. 1988;274:168–77.

    Article  CAS  PubMed  Google Scholar 

  13. Silver RA, Momiyama A, Cull-Candy SG. Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses. J Physiol. 1998;510:881–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Knöpfel T, Vranesic I, Staub C, Gähwiler BH. Climbing fibre responses in olivo-cerebellar slice cultures. II. Dynamics of cytosolic calcium in Purkinje cells. Eur J Neurosci. 1991;3:343–8.

    Article  PubMed  Google Scholar 

  15. 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;68:1178–89.

    Article  CAS  PubMed  Google Scholar 

  16. Canepari M, Vogt KE. Dendritic spike saturation of endogenous calcium buffer and induction of postsynaptic cerebellar LTP. PLoS One. 2008;3:e4011.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Ait Ouares K, Filipis L, Tzilivaki A, Poirazi P, Canepari M. Two distinct sets of Ca2+ and K+ channels are activated at different membrane potentials by the climbing Fiber synaptic potential in Purkinje neuron dendrites. J Neurosci. 2019;39:1969–81.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fierro L, Llano I. High endogenous calcium buffering in Purkinje cells from rat cerebellar slices. J Physiol. 1996;496:617–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bastianelli E. Distribution of calcium-binding proteins in the cerebellum. Cerebellum. 2003;2:242–62.

    Article  CAS  PubMed  Google Scholar 

  20. Schmidt H, Stiefel KM, Racay P, Schwaller B, Eilers J. Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k. J Physiol. 2003;551:13–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Maeda H, Ellis-Davies GC, Ito K, Miyashita Y, Kasai H. Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons. Neuron. 1999;24:989–1002.

    Article  CAS  PubMed  Google Scholar 

  22. Otsu Y, Marcaggi P, Feltz A, Isope P, Kollo M, Nusser Z, et al. Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites. Neuron. 2014;84:137–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hildebrand ME, Isope P, Miyazaki T, Nakaya T, Garcia E, Feltz A, et al. Functional coupling between mGluR1 and Cav3.1 T-type calcium channels contributes to parallel fiber-induced fast calcium signaling within Purkinje cell dendritic spines. J Neurosci. 2009;29:9668–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Isope P, Hildebrand ME, Snutch TP. Contributions of T-type voltage-gated calcium channels to postsynaptic calcium signaling within Purkinje neurons. Cerebellum. 2012;11:651–65.

    Article  CAS  PubMed  Google Scholar 

  25. Canepari M, Ogden D. Evidence for protein tyrosine phosphatase, tyrosine kinase, G-protein regulation of the parallel fiber metabotropic slow EPSC of rat cerebellar Purkinje neurons. J Neurosci. 2003;23:4066–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Anwar H, Hong S, De Schutter E. Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells. Cerebellum. 2012;11:681–93.

    Article  CAS  PubMed  Google Scholar 

  27. Canepari M, Papageorgiou G, Corrie JET, Watkins C, Ogden D. The conductance underlying the parallel fibre slow EPSP in rat cerebellar Purkinje neurones studied with photolytic release of l-glutamate. J Physiol. 2001;533:765–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Canepari M, Auger C, Ogden D. Ca2+ ion permeability and single-channel properties of the metabotropic slow EPSC of rat Purkinje neurons. J Neurosci. 2004;24:3563–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, et al. TRPC3 channels are required for synaptic transmission and motor coordination. Neuron. 2008;59:392–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ady V, Perroy J, Tricoire L, Piochon C, Dadak S, Chen X, et al. Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO Rep. 2014;15:103–9.

    Article  CAS  PubMed  Google Scholar 

  31. Schmidt H, Eilers J. Spine neck geometry determines spino-dendritic cross-talk in the presence of mobile endogenous calcium binding proteins. J Comput Neurosci. 2009;27:229–43.

    Article  PubMed  Google Scholar 

  32. Schmidt H, Kunerth S, Wilms C, Strotmann R, Eilers J. Spino-dendritic cross-talk in rodent Purkinje neurons mediated by endogenous Ca2+-binding proteins. J Physiol. 2007;581:619–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Loewenstein Y, Mahon S, Chadderton P, Kitamura K, Sompolinsky H, Yarom Y, et al. Bistability of cerebellar Purkinje cells modulated by sensory stimulation. Nat Neurosci. 2005;8:202–11.

    Article  CAS  PubMed  Google Scholar 

  34. Kitamura K, Judkewitz B, Kano M, Denk W, Häusser M. Targeted patch-clamp recordings and single-cell electroporation of unlabeled neurons in vivo. Nat Methods. 2008;5:61–7.

    Article  CAS  PubMed  Google Scholar 

  35. Arlt C, Häusser M. Microcircuit rules governing impact of single interneurons on Purkinje cell output in vivo. Cell Rep. 2020;30:3020–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Williams SR, Christensen SR, Stuart GJ, Häusser M. Membrane potential bistability is controlled by the hyperpolarization- activated current I(H) in rat cerebellar Purkinje neurons in vitro. J Physiol. 2002;539:469–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yuen GL, Hockberger PE, Houk JC. Bistability in cerebellar Purkinje cell dendrites modelled with high- threshold calcium and delayed-rectifier potassium channels. Biol Cybern. 1995;73:375–88.

    Article  CAS  PubMed  Google Scholar 

  38. Arancillo M, White JJ, Lin T, Stay TL, Sillitoe RV. In vivo analysis of Purkinje cell firing properties during postnatal mouse development. J Neurophysiol. 2015;113:578–91.

    Article  PubMed  Google Scholar 

  39. Zhou H, Lin Z, Voges K, Ju C, Gao Z, Bosman LW, et al. Cerebellar modules operate at different frequencies. Elife. 2014;3:e02536.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Wu B, Blot FG, Wong AB, Osório C, Adolfs Y, Pasterkamp RJ, et al. TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells. Elife. 2019;8:e45590.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rancz EA, Häusser M. Dendritic calcium spikes are tunable triggers of cannabinoid release and short-term synaptic plasticity in cerebellar Purkinje neurons. J Neurosci. 2006;26:5428–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wulff P, Schonewille M, Renzi M, Viltono L, Sassoè-Pognetto M, Badura A, et al. Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci. 2009;12:1042–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Blazquez PM, Yakusheva TA. GABA-A inhibition shapes the spatial and temporal response properties of Purkinje cells in the macaque cerebellum. Cell Rep. 2015;11:1043–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rowan MJM, Bonnan A, Zhang K, Amat SB, Kikuchi C, Taniguchi H, et al. Graded control of climbing-fiber-mediated plasticity and learning by inhibition in the cerebellum. Neuron. 2018;99:999–1015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gaffield MA, Rowan MJM, Amat SB, Hirai H, Christie JM. Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during practiced movements. Elife. 2018;7:e36246.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kuo CC, Yang S. Recovery from inactivation of t-type ca2+ channels in rat thalamic neurons. J Neurosci. 2001;21:1884–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Szapiro G, Barbour B. Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover. Nat Neurosci. 2007;10:735–42.

    Article  CAS  PubMed  Google Scholar 

  48. Hosy E, Piochon C, Teuling E, Rinaldo L, Hansel C. SK2 channel expression and function in cerebellar Purkinje cells. J Physiol. 2011;589:3433–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cingolani LA, Gymnopoulos M, Boccaccio A, Stocker M, Pedarzani P. Developmental regulation of small-conductance Ca2+−activated K+ channel expression and function in rat Purkinje neurons. J Neurosci. 2002;22:4456–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Luján R, Aguado C, Ciruela F, Arus XM, Martín-Belmonte A, Alfaro-Ruiz R, et al. SK2 channels associate with mGlu receptors and CaV2.1 channels in Purkinje cells. Front Cell Neurosci. 2018;12:311.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Titley HK, Watkins GV, Lin C, Weiss C, McCarthy M, Disterhoft JF, et al. Intrinsic excitability increase in cerebellar Purkinje cells after delay eye-blink conditioning in mice. J Neurosci. 2020;40:2038–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Indriati DW, Kamasawa N, Matsui K, Meredith AL, Watanabe M, Shigemoto R. Quantitative localization of Cav2.1 (P/Q-type) voltage-dependent calcium channels in Purkinje cells: somatodendritic gradient and distinct somatic coclustering with calcium-activated potassium channels. J Neurosci. 2013;33:3668–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Canepari M, Ogden D. Kinetic, pharmacological and activity-dependent separation of two Ca2+ signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones. J Physiol. 2006;573:65–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Maeda N, Kawasaki T, Nakade S, Yokota N, Taguchi T, Kasai M, et al. Structural and functional characterization of inositol 1,4,5-trisphosphate receptor channel from mouse cerebellum. J Biol Chem. 1991;266:1109–16.

    Article  CAS  PubMed  Google Scholar 

  55. Finch EA, Augustine GJ. Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature. 1998;396:753–6.

    Article  CAS  PubMed  Google Scholar 

  56. Takechi H, Eilers J, Konnerth A. A new class of synaptic response involving calcium release in dendritic spines. Nature. n.d.;396:757–60.

  57. Khodakhah K, Armstrong CM. Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons. Proc Natl Acad Sci U S A. 1997;94:14009–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 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.

  59. Kano M, Garaschuk O, Verkhratsky A, Konnerth A. Ryanodine receptor-mediated intracellular calcium release in rat cerebellar Purkinje neurones. J Physiol. 1995;487:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kohda K, Inoue T, Mikoshiba K. Ca2+ release from Ca2+ stores, particularly from ryanodine-sensitive Ca2+ stores, is required for the induction of LTD in cultured cerebellar Purkinje cells. J Neurophysiol. 1995;74:2184–8.

    Article  CAS  PubMed  Google Scholar 

  61. Johansson F, Carlsson HA, Rasmussen A, Yeo CH, Hesslow G. Activation of a temporal memory in Purkinje cells by the mGluR7 receptor. Cell Rep. 2015;13:1741–6.

    Article  CAS  PubMed  Google Scholar 

  62. Niswender CM, Johnson KA, Luo Q, Ayala JE, Kim C, Conn PJ, et al. A novel assay of Gi/o-linked G protein-coupled receptor coupling to potassium channels provides new insights into the pharmacology of the group III metabotropic glutamate receptors. Mol Pharmacol. 2008;73:1213–24.

    Article  CAS  PubMed  Google Scholar 

  63. Aguado C, Colón J, Ciruela F, Schlaudraff F, Cabañero MJ, Perry C, et al. Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. J Neurochem. 2008;105:497–511.

    Article  CAS  PubMed  Google Scholar 

  64. Tabata T, Haruki S, Nakayama H, Kano M. GABAergic activation of an inwardly rectifying K+ current in mouse cerebellar Purkinje cells. J Physiol. 2005;563:443–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Konnerth A, Dreessen J, Augustine GJ. Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells. Proc Natl Acad Sci U S A. 1992;89:7051–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Karachot L, Kado RT, Ito M. Stimulus parameters for induction of long-term depression in in vitro rat Purkinje cells. Neurosci Res. 1995;21:161–8.

    Article  Google Scholar 

  67. Safo PK, Regehr WG. Endocannabinoids control the induction of cerebellar LTD. Neuron. 2005;48:647–59.

    Article  CAS  PubMed  Google Scholar 

  68. Lev-Ram V, Wong ST, Storm DR, Tsien RY. A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP. Proc Natl Acad Sci U S A. 2002;99:8389–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Coesmans M, Weber JT, De Zeeuw CI, Hansel C. Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron. 2004;18:691–700.

    Article  Google Scholar 

  70. Hartell NA. Strong activation of parallel fibers produces localized calcium transients and a form of LTD that spreads to distant synapses. Neuron. 1996;16:601–10.

    Article  CAS  PubMed  Google Scholar 

  71. Bienenstock EL, Cooper LN, Munro PW. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci. 1982;2:32–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 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;372:237–43.

    Article  CAS  PubMed  Google Scholar 

  73. 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;79:377–88.

    Article  CAS  PubMed  Google Scholar 

  74. Hartell NA. Induction of cerebellar long-term depression requires activation of glutamate metabotropic receptors. NeuroReport. 1994;5:913–6.

    Article  CAS  PubMed  Google Scholar 

  75. Marcaggi P, Attwell D. Short- and long-term depression of rat cerebellar parallel fibre synaptic transmission mediated by synaptic crosstalk. J Physiol. 2007;578:545–50.

    Article  CAS  PubMed  Google Scholar 

  76. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RA, Somogyi P. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron. 1993;11:771–87.

    Article  CAS  PubMed  Google Scholar 

  77. Marcaggi P, Attwell D. Endocannabinoid signaling depends on the spatial pattern of synapse activation. Nat Neurosci. 2005;8:776–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bower JM. The organization of cerebellar cortical circuitry revisited: implications for function. Ann N Y Acad Sci. 2002;978:135–55.

    Article  PubMed  Google Scholar 

  79. Welsh JP, Yamaguchi H, Zeng XH, Kojo M, Nakada Y, Takagi A, et al. Normal motor learning during pharmacological prevention of Purkinje cell long-term depression. Proc Natl Acad Sci U S A. 2005;102:17166–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Schonewille M, Gao Z, Boele HJ, Veloz MF, Amerika WE, Simek AA, et al. Reevaluating the role of LTD in cerebellar motor learning. Neuron. 2011;70:43–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tanaka S, Kawaguchi SY, Shioi G, Hirano T. Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex. J Neurosci. 2013;33:17209–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ramakrishnan KB, Voges K, De Propris L, De Zeeuw CI, D’Angelo E. Tactile stimulation evokes long-lasting potentiation of Purkinje cell discharge in vivo. Front Cell Neurosci. 2016;10:36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 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  CAS  PubMed  Google Scholar 

  84. Qiu DL, Knöpfel T. An NMDA receptor/nitric oxide cascade in presynaptic parallel fiber-Purkinje neuron long-term potentiation. J Neurosci. 2007;27:3408–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Casado M, Isope P, Ascher P. Involvement of presynaptic N-methyl-D-aspartate receptors in cerebellar long-term depression. Neuron. 2002;33:123–30.

    Article  CAS  PubMed  Google Scholar 

  86. Bouvier G, Higgins D, Spolidoro M, Carrel D, Mathieu B, Léna C, et al. Burst-dependent bidirectional plasticity in the cerebellum is driven by presynaptic NMDA receptors. Cell Rep. 2016;15:104–16.

    Article  CAS  PubMed  Google Scholar 

  87. Ogasawara H, Doi T, Doya K, Kawato M. Nitric oxide regulates input specificity of long-term depression and context dependence of cerebellar learning. PLoS Comput Biol. 2007;3:e179.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Carey MR, Myoga MH, McDaniels KR, Marsicano G, Lutz B, Mackie K, et al. Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses. J Neurophysiol. 2011;105:958–63.

    Article  CAS  PubMed  Google Scholar 

  89. Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron. 2001;29:717–27.

    Article  CAS  PubMed  Google Scholar 

  90. Maejima T, Hashimoto K, Yoshida T, Aiba A, Kano M. Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors. Neuron. 2001;31:463–75.

    Article  CAS  PubMed  Google Scholar 

  91. Wang DJ, Su LD, Wang YN, Yang D, Sun CL, Zhou L, et al. Long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses requires presynaptic and postsynaptic signaling cascades. J Neurosci. 2014;34:2355–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Suvrathan A, Payne HL, Raymond JL. Timing rules for synaptic plasticity matched to behavioral function. Neuron. 2016;92:959–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hirano T. Regulation and interaction of multiple types of synaptic plasticity in a Purkinje neuron and their contribution to motor learning. Cerebellum. 2018;17:756–65.

    Article  PubMed  Google Scholar 

  94. Zang Y, De Schutter E. Climbing fibers provide graded error signals in cerebellar learning. Front Syst Neurosci. 2019;13:46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dean P, Porrill J, Stone JV. Visual awareness and the cerebellum: possible role of decorrelation control. Prog Brain Res. 2004;144:61–75.

    Article  PubMed  Google Scholar 

  96. Dean P, Porrill J, Stone JV. Decorrelation control by the cerebellum achieves oculomotor plant compensation in simulated vestibulo-ocular reflex. Proc Biol Sci. 2002;269:1895–904.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bouvier G, Aljadeff J, Clopath C, Bimbard C, Ranft J, Blot A, et al. Cerebellar learning using perturbations. Elife. 2018;7:e31599.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Titley HK, Kislin M, Simmons DH, Wang SS, Hansel C. Complex spike clusters and false-positive rejection in a cerebellar supervised learning rule. J Physiol. 2019;597:4387–406.

    Article  CAS  PubMed  Google Scholar 

  99. Titley HK, Brunel N, Hansel C. Toward a Neurocentric view of learning. Neuron. 2017;95:19–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Johansson F. Intrinsic memory of temporal intervals in cerebellar Purkinje cells. Neurobiol Learn Mem. 2019;166:107103.

    Article  PubMed  Google Scholar 

  101. Roome CG, Kuhn B. Simultaneous dendritic voltage and calcium imaging and somatic recording from Purkinje neurons in awake mice. Nat Commun. 2018;9:3388.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Villette V, Chavarha M, Dimov IK, Bradley J, Pradhan L, Mathieu B, et al. Ultrafast two-photon imaging of a high-gain voltage Indicator in awake behaving mice. Cell. 2019;179:1590–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Agence Nationale de la Recherche through the Labex Ion Channels Science and Therapeutics: program number ANR-11-LABX-0015.

Author information

Authors and Affiliations

Authors

Contributions

MC wrote the paper.

Corresponding author

Correspondence to Marco Canepari.

Ethics declarations

Conflict of Interest

The author declares that he has no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Canepari, M. Is Purkinje Neuron Hyperpolarisation Important for Cerebellar Synaptic Plasticity? A Retrospective and Prospective Analysis. Cerebellum 19, 869–878 (2020). https://doi.org/10.1007/s12311-020-01164-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-020-01164-0

Keywords

Navigation