The Cerebellum

, Volume 16, Issue 1, pp 230–252 | Cite as

The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper

  • Eric J. Lang
  • Richard Apps
  • Fredrik Bengtsson
  • Nadia L Cerminara
  • Chris I De Zeeuw
  • Timothy J. Ebner
  • Detlef H. Heck
  • Dieter Jaeger
  • Henrik Jörntell
  • Mitsuo Kawato
  • Thomas S. Otis
  • Ozgecan Ozyildirim
  • Laurentiu S. Popa
  • Alexander M. B. Reeves
  • Nicolas Schweighofer
  • Izumi Sugihara
  • Jianqiang Xiao
Consensus Paper


For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system’s primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less suitable for one or the other of these functions, and why having multiple functions makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest that it has the potential to act in both the motor learning and motor control functions of the cerebellum.


Cerebellum Inferior olive Complex spike Purkinje cell Synchrony Motor control Motor learning 


Compliance with Ethical Standards

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed, and all procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Llinás R. The noncontinuous nature of movement execution. In: Humphrey DR, Freund H-J, editors. Motor control: concepts and issues. New York: Wiley; 1991. p. 223–42.Google Scholar
  2. 2.
    Ito M. Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev. 2001;81:1143–95.PubMedGoogle Scholar
  3. 3.
    Llinás RR. The olivo-cerebellar system: a key to understanding the functional significance of intrinsic oscillatory brain properties. Front Neural Circuits. 2013;7:96.PubMedGoogle Scholar
  4. 4.
    Marr D. A theory of cerebellar cortex. J Physiol Lond. 1969;202:437–70.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Albus JS. A theory of cerebellar function. Math Biosci. 1971;10:25–61.CrossRefGoogle Scholar
  6. 6.
    Keating JG, Thach WT. Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell complex spike discharge in the awake behaving monkey is random. J Neurophysiol. 1995;73:1329–40.PubMedGoogle Scholar
  7. 7.
    Hansel C, Linden DJ, D’Angelo E. Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci. 2001;4:467–75.PubMedGoogle Scholar
  8. 8.
    Gao Z, van Beugen BJ, De Zeeuw CI. Distributed synergistic plasticity and cerebellar learning. Nat Rev Neurosci. 2012;13:619–35.PubMedCrossRefGoogle Scholar
  9. 9.
    Aizenman CD, Manis PB, Linden DJ. Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron. 1998;21:827–35.PubMedCrossRefGoogle Scholar
  10. 10.
    Popa LS, Hewitt AL, Ebner TJ. Predictive and feedback performance errors are signaled in the simple spike discharge of individual Purkinje cells. J Neurosci. 2012;32:15345–58.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Wilson WC, Magoun HW. The functional significance of the inferior olive in the cat. J Comp Neurol. 1945;83:69–77.CrossRefGoogle Scholar
  12. 12.
    Murphy MG, O’Leary JL. Neurological deficit in cats with lesions of the olivocebellar system. Arch Neurol. 1971;24:145–57.PubMedCrossRefGoogle Scholar
  13. 13.
    Soechting JF, Ranish NA, Palminteri R, Terzuolo CA. Changes in a motor pattern following cerebellar and olivary lesions in the squirrel monkey. Brain Res. 1976;105:21–44.PubMedCrossRefGoogle Scholar
  14. 14.
    Kennedy PR, Ross HG, Brooks VB. Participation of the principal olivary nucleus in neocerebellar motor control. Exp Brain Res. 1982;47:95–104.PubMedGoogle Scholar
  15. 15.
    Seoane A, Apps R, Balbuena E, Herrero L, Llorens J. Differential effects of trans-crotononitrile and 3-acetylpyridine on inferior olive integrity and behavioural performance in the rat. Eur J Neurosci. 2005;22:880–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Horn KM, Deep A, Gibson AR. Progressive limb ataxia following inferior olive lesions. J Physiol Lond. 2013;591:5475–89.PubMedCrossRefGoogle Scholar
  17. 17.
    Colin F, Manil J, Desclin JC. The olivocerebellar system. I. Delayed and slow inhibitory effects: an overlooked salient feature of cerebellar climbing fibers. Brain Res. 1980;187:3–27.PubMedCrossRefGoogle Scholar
  18. 18.
    Savio T, Tempia F. On the Purkinje cell activity increase induced by suppression of inferior olive activity. Exp Brain Res. 1985;57:456–63.PubMedCrossRefGoogle Scholar
  19. 19.
    Batini C, Billard JM. Release of cerebellar inhibition by climbing fiber deafferentation. Exp Brain Res. 1985;57:370–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Barmack NH, Yakhnitsa V. Cerebellar climbing fibers modulate simple spikes in Purkinje cells. J Neurosci. 2003;23:7904–16.PubMedGoogle Scholar
  21. 21.
    Cerminara NL, Rawson JA. Evidence that climbing fibers control an intrinsic spike generator in cerebellar Purkinje cells. J Neurosci. 2004;24:4510–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Mathews PJ, Lee KH, Peng Z, Houser CR, Otis TS. Effects of climbing fiber driven inhibition on Purkinje neuron spiking. J Neurosci. 2012;32:17988–97.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Lang EJ, Sugihara I, Welsh JP, Llinas R. Patterns of spontaneous Purkinje cell complex spike activity in the awake rat. J Neurosci. 1999;19:2728–39.PubMedGoogle Scholar
  24. 24.
    Sasaki K, Bower JM, Llinas R. Multiple Purkinje cell recording in rodent cerebellar cortex. Eur J Neurosci. 1989;1:572–86.PubMedCrossRefGoogle Scholar
  25. 25.
    Bell CC, Kawasaki T. Relations among climbing fiber responses of nearby Purkinje cells. J Neurophysiol. 1972;35:155–69.PubMedGoogle Scholar
  26. 26.
    Ozden I, Sullivan MR, Lee HM, Wang SS. Reliable coding emerges from coactivation of climbing fibers in microbands of cerebellar Purkinje neurons. J Neurosci. 2009;29:10463–73.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Welsh JP, Lang EJ, Sugihara I, Llinás R. Dynamic organization of motor control within the olivocerebellar system. Nature. 1995;374:453–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Lang EJ, Sugihara I, Llinás R. Olivocerebellar modulation of motor cortex ability to generate vibrissal movements in rats. J Physiol Lond. 2006;571:101–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Van Der Giessen RS, Koekkoek SK, van Dorp S, De Gruijl JR, Cupido A, Khosrovani S, et al. Role of olivary electrical coupling in cerebellar motor learning. Neuron. 2008;58:599–612.CrossRefGoogle Scholar
  30. 30.
    Mukamel EA, Nimmerjahn A, Schnitzer MJ. Automated analysis of cellular signals from large-scale calcium imaging data. Neuron. 2009;63:747–60.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Hoogland TM, De Gruijl JR, Witter L, Canto CB, De Zeeuw CI. Role of synchronous activation of cerebellar Purkinje cell ensembles in multi-joint movement control. Curr Biol. 2015;25:1157–65.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Blenkinsop TA, Lang EJ. Synaptic action of the olivocerebellar system on cerebellar nuclear spike activity. J Neurosci. 2011;31:14708–20.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Bengtsson F, Ekerot CF, Jorntell H. In vivo analysis of inhibitory synaptic inputs and rebounds in deep cerebellar nuclear neurons. PLoS One. 2011;6, e18822.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Tang T, Suh CY, Blenkinsop TA, Lang EJ. Synchrony is key: complex spike inhibition of the deep cerebellar nuclei. Cerebellum. 2016;15:10–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Otis TS, Mathews PJ, Lee KH, Maiz J. How do climbing fibers teach? Front Neural Circuits. 2012;6:95.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Shadmehr R, Smith MA, Krakauer JW. Error correction, sensory prediction, and adaptation in motor control. Annu Rev Neurosci. 2010;33:89–108.PubMedCrossRefGoogle Scholar
  37. 37.
    Wolpert DM, Miall RC. Forward models for physiological motor control. Neural Netw. 1996;9:1265–79.PubMedCrossRefGoogle Scholar
  38. 38.
    Oscarsson O. Functional organization of olivary projection to the cerebellar anterior lobe. In: Courville J, De Montigny C, Lamarre Y, editors. The inferior olivary nucleus: anatomy and physiology. New York: Raven; 1980. p. 279–89.Google Scholar
  39. 39.
    Graf W, Simpson JI, Leonard CS. Spatial organization of visual messages of the rabbit’s cerebellar flocculus. II. Complex and simple spike responses of Purkinje cells. J Neurophysiol. 1988;60:2091–121.PubMedGoogle Scholar
  40. 40.
    Soetedjo R, Kojima Y, Fuchs AF. Complex spike activity in the oculomotor vermis of the cerebellum: a vectorial error signal for saccade motor learning? J Neurophysiol. 2008;100:1949–66.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Medina JF, Lisberger SG. Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys. Nat Neurosci. 2008;11:1185–92.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Yang Y, Lisberger SG. Purkinje-cell plasticity and cerebellar motor learning are graded by complex-spike duration. Nature. 2014;510:529–32.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Guo CC, Ke MC, Raymond JL. Cerebellar encoding of multiple candidate error cues in the service of motor learning. J Neurosci. 2014;34:9880–90.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Ebner TJ, Hewitt AL, Popa LS. What features of limb movements are encoded in the discharge of cerebellar neurons? Cerebellum. 2011;10:683–93.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Popa LS, Streng ML, Hewitt AL, Ebner TJ. The errors of our ways: understanding error representations in cerebellar-dependent motor learning. Cerebellum. 2016;15:93–103.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Hewitt AL, Popa LS, Ebner TJ. Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation. J Neurosci. 2015;35:1106–24.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kimpo RR, Rinaldi JM, Kim CK, Payne HL, Raymond JL. Gating of neural error signals during motor learning. Elife. 2014;3, e02076.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Nguyen-Vu TD, Kimpo RR, Rinaldi JM, Kohli A, Zeng H, Deisseroth K, et al. Cerebellar Purkinje cell activity drives motor learning. Nat Neurosci. 2013;16:1734–6.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    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.PubMedCrossRefGoogle Scholar
  50. 50.
    Han VZ, Zhang Y, Bell CC, Hansel C. Synaptic plasticity and calcium signaling in Purkinje cells of the central cerebellar lobes of mormyrid fish. J Neurosci. 2007;27:13499–512.PubMedCrossRefGoogle Scholar
  51. 51.
    Wang X, Chen G, Gao W, Ebner T. Long-term potentiation of the responses to parallel fiber stimulation in mouse cerebellar cortex in vivo. Neuroscience. 2009;162:713–22.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Wang X, Chen G, Gao W, Ebner TJ. Parasagittally aligned, mGluR1-dependent patches are evoked at long latencies by parallel fiber stimulation in the mouse cerebellar cortex in vivo. J Neurophysiol. 2011;105:1732–46.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Roitman AV, Pasalar S, Ebner TJ. Single trial coupling of Purkinje cell activity to speed and error signals during circular manual tracking. Exp Brain Res. 2009;192:241–51.PubMedCrossRefGoogle Scholar
  54. 54.
    Ke MC, Guo CC, Raymond JL. Elimination of climbing fiber instructive signals during motor learning. Nat Neurosci. 2009;12:1171–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Hewitt AL, Popa LS, Pasalar S, Hendrix CM, Ebner TJ. Representation of limb kinematics in Purkinje cell simple spike discharge is conserved across multiple tasks. J Neurophysiol. 2011;106:2232–47.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Popa LS, Hewitt AL, Ebner TJ. Purkinje cell simple spike discharge encodes error signals consistent with a forward internal model. Cerebellum. 2013;12:331–3.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Marshall SP, Lang EJ. Local changes in the excitability of the cerebellar cortex produce spatially restricted changes in complex spike synchrony. J Neurosci. 2009;29:14352–62.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Chaumont J, Guyon N, Valera AM, Dugue GP, Popa D, Marcaggi P, et al. Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge. Proc Natl Acad Sci U S A. 2013;110:16223–8.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Witter L, Canto CB, Hoogland TM, de Gruijl JR, De Zeeuw CI. Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation. Front Neural Circuits. 2013;7:133.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Jirenhed DA, Bengtsson F, Hesslow G. Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. J Neurosci. 2007;27:2493–502.PubMedCrossRefGoogle Scholar
  61. 61.
    Jorntell H, Ekerot CF. Reciprocal bidirectional plasticity of parallel fiber receptive fields in cerebellar Purkinje cells and their afferent interneurons. Neuron. 2002;34:797–806.PubMedCrossRefGoogle Scholar
  62. 62.
    Mauk MD, Steinmetz JE, Thompson RF. Classical conditioning using stimulation of the inferior olive as the unconditioned stimulus. Proc Natl Acad Sci U S A. 1986;83:5349–53.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Maiz J, Karakossian MH, Pakaprot N, Robleto K, Thompson RF, Otis TS. Prolonging the postcomplex spike pause speeds eyeblink conditioning. Proc Natl Acad Sci U S A. 2012;109:16726–30.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Lee KH, Mathews PJ, Reeves AM, Choe KY, Jami SA, Serrano RE, et al. Circuit mechanisms underlying motor memory formation in the cerebellum. Neuron. 2015;86:529–40.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Cooke SF, Attwell PJ, Yeo CH. Temporal properties of cerebellar-dependent memory consolidation. J Neurosci. 2004;24:2934–41.PubMedCrossRefGoogle Scholar
  66. 66.
    Kassardjian CD, Tan YF, Chung JY, Heskin R, Peterson MJ, Broussard DM. The site of a motor memory shifts with consolidation. J Neurosci. 2005;25:7979–85.PubMedCrossRefGoogle Scholar
  67. 67.
    Okamoto T, Shirao T, Shutoh F, Suzuki T, Nagao S. Post-training cerebellar cortical activity plays an important role for consolidation of memory of cerebellum-dependent motor learning. Neurosci Lett. 2011;504:53–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Shutoh F, Ohki M, Kitazawa H, Itohara S, Nagao S. Memory trace of motor learning shifts transsynaptically from cerebellar cortex to nuclei for consolidation. Neuroscience. 2006;139:767–77.PubMedCrossRefGoogle Scholar
  69. 69.
    Titley HK, Heskin-Sweezie R, Chung JY, Kassardjian CD, Razik F, Broussard DM. Rapid consolidation of motor memory in the vestibuloocular reflex. J Neurophysiol. 2007;98:3809–12.PubMedCrossRefGoogle Scholar
  70. 70.
    Medina JF. The multiple roles of Purkinje cells in sensori-motor calibration: to predict, teach and command. Curr Opin Neurobiol. 2011;21:616–22.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Medina JF, Nores WL, Mauk MD. Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature. 2002;416:330–3.PubMedCrossRefGoogle Scholar
  72. 72.
    Wulff P, Schonewille M, Renzi M, Viltono L, Sassoe-Pognetto M, Badura A, et al. Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci. 2009;12:1042–9.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Simpson JI, Alley KE. Visual climbing fiber input to rabbit vestibulo-cerebellum: a source of direction-specific information. Brain Res. 1974;82:302–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Gilbert PFC, Thach WT. Purkinje cell activity during motor learning. Brain Res. 1977;128:309–28.PubMedCrossRefGoogle Scholar
  75. 75.
    Kim JJ, Krupa DJ, Thompson RF. Inhibitory cerebello-olivary projections and blocking effect in classical conditioning. Science. 1998;279:570–3.PubMedCrossRefGoogle Scholar
  76. 76.
    Kitamura K, Hausser M. Dendritic calcium signaling triggered by spontaneous and sensory-evoked climbing fiber input to cerebellar Purkinje cells in vivo. J Neurosci. 2011;31:10847–58.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Tank DW, Sugimori M, Connor JA, Llinas RR. Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice. Science. 1988;242:773–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Ghosh KK, Burns LD, Cocker ED, Nimmerjahn A, Ziv Y, Gamal AE, et al. Miniaturized integration of a fluorescence microscope. Nat Methods. 2011;8:871–8.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Schultz SR, Kitamura K, Post-Uiterweer A, Krupic J, Hausser M. Spatial pattern coding of sensory information by climbing fiber-evoked calcium signals in networks of neighboring cerebellar Purkinje cells. J Neurosci. 2009;29:8005–15.PubMedCrossRefGoogle Scholar
  80. 80.
    Lisberger SG. Neural basis for motor learning in the vestibuloocular reflex of primates. III. Computational and behavioral analysis of the sites of learning. J Neurophysiol. 1994;72:974–98.PubMedGoogle Scholar
  81. 81.
    Albert NB, Robertson EM, Miall RC. The resting human brain and motor learning. Curr Biol. 2009;19:1023–7.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab. 2012;32:1222–32.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Ito M. The molecular organization of cerebellar long-term depression. Nat Rev Neurosci. 2002;3:896–902.PubMedCrossRefGoogle Scholar
  84. 84.
    Safo P, Regehr WG. Timing dependence of the induction of cerebellar LTD. Neuropharmacology. 2008;54:213–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Wang SS, Denk W, Hausser M. Coincidence detection in single dendritic spines mediated by calcium release. Nat Neurosci. 2000;3:1266–73.PubMedCrossRefGoogle Scholar
  86. 86.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Welsh JP, Yamaguchi H, Zeng X-H, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Medina JF, Nores WL, Ohyama T, Mauk MD. Mechanisms of cerebellar learning suggested by eyelid conditioning. Curr Opin Neurobiol. 2000;10:717–24.PubMedCrossRefGoogle Scholar
  89. 89.
    Miles FA, Lisberger SG. Plasticity in the vestibulo-ocular reflex: a new hypothesis. Annu Rev Neurosci. 1981;4:273–99.PubMedCrossRefGoogle Scholar
  90. 90.
    Ohyama T, Mauk M. Latent acquisition of timed responses in cerebellar cortex. J Neurosci. 2001;21:682–90.PubMedGoogle Scholar
  91. 91.
    Perrett SP, Ruiz BP, Mauk MD. Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci. 1993;13:1708–18.PubMedGoogle Scholar
  92. 92.
    Grasselli G, He Q, Wan V, Adelman JP, Ohtsuki G, Hansel C. Activity-dependent plasticity of spike pauses in cerebellar Purkinje cells. Cell Rep. 2016;14:2546–53.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Lefler Y, Yarom Y, Uusisaari MY. Cerebellar inhibitory input to the inferior olive decreases electrical coupling and blocks subthreshold oscillations. Neuron. 2014;81:1389–400.PubMedCrossRefGoogle Scholar
  94. 94.
    Ruigrok TJH, Voogd J. Organization of projections from the inferior olive to the cerebellar nuclei in the rat. J Comp Neurol. 2000;426:209–28.PubMedCrossRefGoogle Scholar
  95. 95.
    van der Want JJ, Wiklund L, Guegan M, Ruigrok T, Voogd J. Anterograde tracing of the rat olivocerebellar system with Phaseolus vulgaris leucoagglutinin (PHA-L). Demonstration of climbing fiber collateral innervation of the cerebellar nuclei. J Comp Neurol. 1989;288:1–18.PubMedCrossRefGoogle Scholar
  96. 96.
    Wiklund L, Toggenburger G, Cuenod M. Selective retrograde labelling of the rat olivocerebellar climbing fiber system with D-[3H]aspartate. Neuroscience. 1984;13:441–68.PubMedCrossRefGoogle Scholar
  97. 97.
    van der Want JJ, Voogd J. Ultrastructural identification and localization of climbing fiber terminals in the fastigial nucleus of the cat. J Comp Neurol. 1987;258:81–90.PubMedCrossRefGoogle Scholar
  98. 98.
    Kitai ST, McCrea RA, Preston RJ, Bishop GA. Electrophysiological and horseradish peroxidase studies of precerebellar afferents to the nucleus interpositus anterior. I. Climbing fiber system. Brain Res. 1977;122:197–214.PubMedCrossRefGoogle Scholar
  99. 99.
    Ruigrok TJ. Cerebellar nuclei: the olivary connection. Prog Brain Res. 1997;114:167–92.PubMedCrossRefGoogle Scholar
  100. 100.
    Armstrong DM, Cogdell B, Harvey RJ. Responses of interpositus neurones to nerve stimulation in chloralose anaesthetized cats. Brain Res. 1973;55:461–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Rowland NC, Jaeger D. Responses to tactile stimulation in deep cerebellar nucleus neurons result from recurrent activation in multiple pathways. J Neurophysiol. 2008;99:704–17.PubMedCrossRefGoogle Scholar
  102. 102.
    Hoebeek FE, Witter L, Ruigrok TJ, De Zeeuw CI. Differential olivo-cerebellar cortical control of rebound activity in the cerebellar nuclei. Proc Natl Acad Sci U S A. 2010;107:8410–5.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Lu H, Yang B, Jaeger D. Cerebellar nuclei neurons show only small excitatory responses to optogenetic olivary stimulation in transgenic mice: in vivo and in vitro studies. Front Neural Circuits. 2016; in press.Google Scholar
  104. 104.
    Pijpers A, Voogd J, Ruigrok TJH. Topography of olivo-cortico-nuclear modules in the intermediate cerebellum of the rat. J Comp Neurol. 2005;492:193–213.PubMedCrossRefGoogle Scholar
  105. 105.
    Fournier B, Lohof AM, Bower AJ, Mariani J, Sherrard RM. Developmental modifications of olivocerebellar topography: the granuloprival cerebellum reveals multiple routes from the inferior olive. J Comp Neurol. 2005;490:85–97.PubMedCrossRefGoogle Scholar
  106. 106.
    Person AL, Raman IM. Deactivation of L-type Ca current by inhibition controls LTP at excitatory synapses in the cerebellar nuclei. Neuron. 2010;66:550–9.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Pugh JR, Raman IM. Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition. J Neurosci. 2008;28:10549–60.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Andersson G, Oscarsson O. Climbing fiber microzones in cerebellar vermis and their projection to different groups of cells in the lateral vestibular nucleus. Exp Brain Res. 1978;32:565–79.PubMedGoogle Scholar
  109. 109.
    Ito M. The cerebellum and neural control. New York: Raven; 1984.Google Scholar
  110. 110.
    Garwicz M, Ekerot CF. Topographical organization of the cerebellar cortical projection to nucleus interpositus anterior in the cat. J Physiol Lond. 1994;474:245–60.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Shinoda Y, Sugihara I, Wu HS, Sugiuchi Y. The entire trajectory of single climbing and mossy fibers in the cerebellar nuclei and cortex. Prog Brain Res. 2000;124:173–86.PubMedCrossRefGoogle Scholar
  112. 112.
    Bengtsson F, Jorntell H. Specific relationship between excitatory inputs and climbing fiber receptive fields in deep cerebellar nuclear neurons. PLoS One. 2014;9, e84616.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    van Kan PL, Houk JC, Gibson AR. Output organization of intermediate cerebellum of the monkey. J Neurophysiol. 1993;69:57–73.PubMedGoogle Scholar
  114. 114.
    Jahnsen H. Electrophysiological characteristics of neurones in the guinea-pig deep cerebellar nuclei in vitro. J Physiol Lond. 1986;372:129–47.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Llinás R, Muhlethaler M. Electrophysiology of guinea-pig cerebellar nuclear cells in the in vitro brain stem-cerebellar preparation. J Physiol Lond. 1988;404:241–58.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000;20:9004–16.PubMedGoogle Scholar
  117. 117.
    McKay BE, Molineux ML, Mehaffey WH, Turner RW. Kv1 K+ channels control Purkinje cell output to facilitate postsynaptic rebound discharge in deep cerebellar neurons. J Neurosci. 2005;25:1481–92.PubMedCrossRefGoogle Scholar
  118. 118.
    Armstrong DM, Rawson JA. Responses of neurones in nucleus interpositus of the cerebellum to cutaneous nerve volleys in the awake cat. J Physiol Lond. 1979;289:403–23.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Hesslow G. Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. J Physiol Lond. 1994;476:245–56.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Alvina K, Walter JT, Kohn A, Ellis-Davies G, Khodakhah K. Questioning the role of rebound firing in the cerebellum. Nat Neurosci. 2008;11:1256–8.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Horn KM, Van Kan PL, Gibson AR. Reduction of rostral dorsal accessory olive responses during reaching. J Neurophysiol. 1996;76:4140–51.PubMedGoogle Scholar
  122. 122.
    Shambes GM, Gibson JM, Welker W. Fractured somatotopy in granule cell tactile areas of rat cerebellar hemispheres revealed by micromapping. Brain Behav Evol. 1978;15:94–140.PubMedCrossRefGoogle Scholar
  123. 123.
    Chen S, Augustine GJ, Chadderton P. The cerebellum linearly encodes whisker position during voluntary movement. Elife. 2016;5.Google Scholar
  124. 124.
    Bryant JL, Boughter JD, Gong S, LeDoux MS, Heck DH. Cerebellar cortical output encodes temporal aspects of rhythmic licking movements and is necessary for normal licking frequency. Eur J Neurosci. 2010;32:41–52.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Cao Y, Maran SK, Dhamala M, Jaeger D, Heck DH. Behavior related pauses in simple spike activity of mouse Purkinje cells are linked to spike rate modulation. J Neurosci. 2012;32:8678–85.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Lu L, Cao Y, Tokita K, Heck DH, Boughter JD. Medial cerebellar nuclear projections and activity patterns link cerebellar output to orofacial and respiratory behavior. Front Neural Circuits. 2013;7:56.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Travers JB, Dinardo LA, Karimnamazi H. Motor and premotor mechanisms of licking. Neurosci Biobehav Rev. 1997;21:631–47.PubMedCrossRefGoogle Scholar
  128. 128.
    Jean A. Brainstem control of swallowing: localization and organization of the central pattern generator for swallowing. In: Taylor A, editor. Neurophysiology of the jaws and teeth. London: Macmillan; 1990. p. 294–321.CrossRefGoogle Scholar
  129. 129.
    Feldman JL, Mitchell GS, Nattie EE. Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci. 2003;26:239–66.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Vajnerova O, Zhuravin IA, Brozek G. Functional ablation of deep cerebellar nuclei temporarily impairs learned coordination of forepaw and tongue movements. Behav Brain Res. 2000;108:189–95.PubMedCrossRefGoogle Scholar
  131. 131.
    Hayar A, Bryant JL, Boughter JD, Heck DH. A low-cost solution to measure mouse licking in an electrophysiological setup with a standard analog-to-digital converter. J Neurosci Methods. 2006;2:203–7.CrossRefGoogle Scholar
  132. 132.
    Weijnen JA, Wouters J, van Hest JM. Interaction between licking and swallowing in the drinking rat. Brain Behav Evol. 1984;25:117–27.PubMedCrossRefGoogle Scholar
  133. 133.
    Welzl H, Bures J. Lick-synchronized breathing in rats. Physiol Behav. 1977;18:751–3.PubMedCrossRefGoogle Scholar
  134. 134.
    Teune TM, van der Burg J, van der Moer J, Voogd J, Ruigrok TJ. Topography of cerebellar nuclear projections to the brain stem in the rat. Prog Brain Res. 2000;124:141–72.PubMedCrossRefGoogle Scholar
  135. 135.
    Eccles JC, Ito M, Szentágothai J. The cerebellum as a neuronal machine. Berlin: Springer; 1967.CrossRefGoogle Scholar
  136. 136.
    Ito M, Yoshida M, Obata K. Monosynaptic inhibition of the intracerebellar nuclei induced rom the cerebellar cortex. Experientia. 1964;20:575–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Ito M, Yoshida M, Obata K, Kawai N, Udo M. Inhibitory control of intracerebellar nuclei by the Purkinje cell axons. Exp Brain Res. 1970;10:64–80.PubMedCrossRefGoogle Scholar
  138. 138.
    Gravel C, Hawkes R. Parasagittal organization of the rat cerebellar cortex: direct comparison of Purkinje cell compartments and the organization of the spinocerebellar projection. J Comp Neurol. 1990;291:79–102.PubMedCrossRefGoogle Scholar
  139. 139.
    Ahn AH, Dziennis S, Hawkes R, Herrup K. The cloning of zebrin II reveals its identity with aldolase C. Development. 1994;120:2081–90.PubMedGoogle Scholar
  140. 140.
    Sarna JR, Marzban H, Watanabe M, Hawkes R. Complementary stripes of phospholipase Cbeta3 and Cbeta4 expression by Purkinje cell subsets in the mouse cerebellum. J Comp Neurol. 2006;496:303–13.PubMedCrossRefGoogle Scholar
  141. 141.
    Dehnes Y, Chaudhry FA, Ullensvang K, Lehre KP, Storm-Mathisen J, Danbolt NC. The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia. J Neurosci. 1998;18:3606–19.PubMedGoogle Scholar
  142. 142.
    Llinás R, Sugimori M. Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J Physiol Lond. 1980;305:171–95.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Llinás R, Sugimori M. Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol Lond. 1980;305:197–213.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    McKay BE, Turner RW. Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells. Eur J Neurosci. 2004;20:729–39.PubMedCrossRefGoogle Scholar
  145. 145.
    Pouille F, Cavelier P, Desplantez T, Beekenkamp H, Craig PJ, Beattie RE, et al. Dendro-somatic distribution of calcium-mediated electrogenesis in purkinje cells from rat cerebellar slice cultures. J Physiol Lond. 2000;527(Pt 2):265–82.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Womack M, Khodakhah K. Active contribution of dendrites to the tonic and trimodal patterns of activity in cerebellar Purkinje neurons. J Neurosci. 2002;22:10603–12.PubMedGoogle Scholar
  147. 147.
    Kim CH, Oh SH, Lee JH, Chang SO, Kim J, Kim SJ. Lobule-specific membrane excitability of cerebellar Purkinje cells. J Physiol Lond. 2012;590:273–88.PubMedCrossRefGoogle Scholar
  148. 148.
    Cerminara NL, Aoki H, Loft M, Sugihara I, Apps R. Structural basis of cerebellar microcircuits in the rat. J Neurosci. 2013;33:16427–42.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Xiao J, Cerminara NL, Kotsurovskyy Y, Aoki H, Burroughs A, Wise AK, et al. Systematic regional variations in Purkinje cell spiking patterns. PLoS One. 2014;9, e105633.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Zhou H, Lin Z, Voges K, Ju C, Gao Z, Bosman LW, et al. Cerebellar modules operate at different frequencies. Elife. 2014;3, e02536.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Paukert M, Huang YH, Tanaka K, Rothstein JD, Bergles DE. Zones of enhanced glutamate release from climbing fibers in the mammalian cerebellum. J Neurosci. 2010;30:7290–9.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Xiao J, Cerminara NL, Aoki H, Sugihara I, Wise A, Sanderson J, et al. Investigation of potential determinants of the complex spike waveform: Zebrin reactivity and simple spike activity. Society for Neuroscience Meeting Abstracts 2012;580.05.Google Scholar
  153. 153.
    Sugihara I, Shinoda Y. Molecular, topographic, and functional organization of the cerebellar cortex: a study with combined aldolase C and olivocerebellar labeling. J Neurosci. 2004;24:8771–85.PubMedCrossRefGoogle Scholar
  154. 154.
    McDevitt CJ, Ebner TJ, Bloedel JR. The changes in Purkinje cell simple spike activity following spontaneous climbing fiber inputs. Brain Res. 1982;237:484–91.PubMedCrossRefGoogle Scholar
  155. 155.
    Kim JJ, Thompson RF. Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning. Trends Neurosci. 1997;20:177–81.PubMedCrossRefGoogle Scholar
  156. 156.
    Yeo CH, Hardiman MJ, Glickstein M. Classical conditioning of the nictitating membrane response of the rabbit. II. Lesions of the cerebellar cortex. Exp Brain Res. 1985;60:99–113.PubMedCrossRefGoogle Scholar
  157. 157.
    Allami N, Paulignan Y, Brovelli A, Boussaoud D. Visuo-motor learning with combination of different rates of motor imagery and physical practice. Exp Brain Res. 2008;184:105–13.PubMedCrossRefGoogle Scholar
  158. 158.
    Lacourse MG, Turner JA, Randolph-Orr E, Schandler SL, Cohen MJ. Cerebral and cerebellar sensorimotor plasticity following motor imagery-based mental practice of a sequential movement. J Rehabil Res Dev. 2004;41:505–24.PubMedCrossRefGoogle Scholar
  159. 159.
    Lang EJ, Tang T, Suh CY, Xiao J, Kotsurovskyy Y, Blenkinsop TA, et al. Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system. Front Syst Neurosci. 2014;8:210.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Llinás R, Volkind RA. The olivo-cerebellar system: functional properties as revealed by harmaline-induced tremor. Exp Brain Res. 1973;18:69–87.PubMedCrossRefGoogle Scholar
  161. 161.
    de Montigny C, Lamarre Y. Rhythmic activity induced by harmaline in the olivo-cerebello-bulbar system of the cat. Brain Res. 1973;53:81–95.PubMedCrossRefGoogle Scholar
  162. 162.
    Sugihara I, Marshall SP, Lang EJ. Relationship of complex spike synchrony to the lobular and longitudinal aldolase C compartments in crus IIA of the cerebellar cortex. J Comp Neurol. 2007;501:13–29.PubMedCrossRefGoogle Scholar
  163. 163.
    Chung SH, Marzban H, Hawkes R. Compartmentation of the cerebellar nuclei of the mouse. Neuroscience. 2009;161:123–38.PubMedCrossRefGoogle Scholar
  164. 164.
    Sugihara I. Compartmentalization of the deep cerebellar nuclei based on afferent projections and aldolase C expression. Cerebellum. 2011;10:449–63.PubMedCrossRefGoogle Scholar
  165. 165.
    Lang EJ, Blenkinsop TA. Control of cerebellar nuclear cells: a direct role for complex spikes? Cerebellum. 2011;10:694–701.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Llinás R, Baker R, Sotelo C. Electrotonic coupling between neurons in cat inferior olive. J Neurophysiol. 1974;37:560–71.PubMedGoogle Scholar
  167. 167.
    Sotelo C, Llinás R, Baker R. Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling. J Neurophysiol. 1974;37:541–59.PubMedGoogle Scholar
  168. 168.
    Blenkinsop TA, Lang EJ. Block of inferior olive gap junctional coupling decreases Purkinje cell complex spike synchrony and rhythmicity. J Neurosci. 2006;26:1739–48.PubMedCrossRefGoogle Scholar
  169. 169.
    Marshall SP, van der Giessen RS, de Zeeuw CI, Lang EJ. Altered olivocerebellar activity patterns in the connexin36 knockout mouse. Cerebellum. 2007;6:287–99.PubMedCrossRefGoogle Scholar
  170. 170.
    Llinás R, Sasaki K. The functional organization of the olivo-cerebellar system as examined by multiple Purkinje cell recordings. Eur J Neurosci. 1989;1:587–602.PubMedCrossRefGoogle Scholar
  171. 171.
    Lang EJ. Organization of olivocerebellar activity in the absence of excitatory glutamatergic input. J Neurosci. 2001;21:1663–75.PubMedGoogle Scholar
  172. 172.
    Lang EJ. GABAergic and glutamatergic modulation of spontaneous and motor-cortex-evoked complex spike activity. J Neurophysiol. 2002;87:1993–2008.PubMedCrossRefGoogle Scholar
  173. 173.
    Lang EJ, Sugihara I, Llinás R. GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat. J Neurophysiol. 1996;76:255–75.PubMedGoogle Scholar
  174. 174.
    Sugihara I, Lang EJ, Llinás R. Serotonin modulation of inferior olivary oscillations and synchronicity: a multiple-electrode study in the rat cerebellum. Eur J Neurosci. 1995;7:521–34.PubMedCrossRefGoogle Scholar
  175. 175.
    Eccles JC, Llinas R, Sasaki K. The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum. J Physiol Lond. 1966;182:268–96.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Crill WE. Unitary multiple-spiked responses in cat inferior olive nucleus. J Neurophysiol. 1970;33:199–209.PubMedGoogle Scholar
  177. 177.
    Armstrong DM, Rawson JA. Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. J Physiol Lond. 1979;289:425–48.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Mathy A, Ho SS, Davie JT, Duguid IC, Clark BA, Hausser M. Encoding of oscillations by axonal bursts in inferior olive neurons. Neuron. 2009;62:388–99.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Rasmussen A, Jirenhed DA, Zucca R, Johansson F, Svensson P, Hesslow G. Number of spikes in climbing fibers determines the direction of cerebellar learning. J Neurosci. 2013;33:13436–40.PubMedCrossRefGoogle Scholar
  180. 180.
    Eccles JC, Llinás R, Sasaki K, Voorhoeve PE. Interaction experiments on the responses evoked in Purkinje cells by climbing fibres. J Physiol Lond. 1966;182:297–315.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Callaway JC, Lasser-Ross N, Ross WN. IPSPs strongly inhibit climbing fiber-activated [Ca2+]i increases in the dendrites of cerebellar Purkinje neurons. J Neurosci. 1995;15:2777–87.PubMedGoogle Scholar
  182. 182.
    Ekerot C-F, Kano M. Long-term depression of parallel fibre synapses following stimulation of climbing fibres. Brain Res. 1985;342:357–60.PubMedCrossRefGoogle Scholar
  183. 183.
    Kawato M. Internal models for motor control and trajectory planning. Curr Opin Neurobiol. 1999;9:718–27.PubMedCrossRefGoogle Scholar
  184. 184.
    Kitazawa S, Kimura T, Yin PB. Cerebellar complex spikes encode both destinations and errors in arm movements. Nature. 1998;392:494–7.PubMedCrossRefGoogle Scholar
  185. 185.
    Tokuda IT, Han CE, Aihara K, Kawato M, Schweighofer N. The role of chaotic resonance in cerebellar learning. Neural Netw Off J Int Neural Netw Soc. 2010;23:836–42.CrossRefGoogle Scholar
  186. 186.
    Tokuda IT, Hoang H, Schweighofer N, Kawato M. Adaptive coupling of inferior olive neurons in cerebellar learning. Neural Netw Off J Int Neural Netw Soc. 2013;47:42–50.CrossRefGoogle Scholar
  187. 187.
    Schweighofer N, Doya K, Fukai H, Chiron JV, Furukawa T, Kawato M. Chaos may enhance information transmission in the inferior olive. Proc Natl Acad Sci U S A. 2004;101:4655–60.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Makarenko V, Llinas R. Experimentally determined chaotic phase synchronization in a neuronal system. Proc Natl Acad Sci U S A. 1998;95:15747–52.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Schweighofer N, Doya K, Kawato M. Electrophysiological properties of inferior olive neurons: a compartmental model. J Neurophysiol. 1999;82:804–17.PubMedGoogle Scholar
  190. 190.
    Nishimura H, Katada N, Aihara K. Coherent response in a chaotic neural network. Neural Process Lett. 2000;12:49–58.CrossRefGoogle Scholar
  191. 191.
    Onizuka M, Hoang H, Kawato M, Tokuda IT, Schweighofer N, Katori Y, et al. Solution to the inverse problem of estimating gap-junctional and inhibitory conductance in inferior olive neurons from spike trains by network model simulation. Neural Netw. 2013;47:51–63.PubMedCrossRefGoogle Scholar
  192. 192.
    Turecek J, Yuen GS, Han VZ, Zeng XH, Bayer KU, Welsh JP. NMDA receptor activation strengthens weak electrical coupling in mammalian brain. Neuron. 2014;81:1375–88.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Kawato M, Kuroda S, Schweighofer N. Cerebellar supervised learning revisited: biophysical modeling and degrees-of-freedom control. Curr Opin Neurobiol. 2011;21:791–800.PubMedCrossRefGoogle Scholar
  194. 194.
    Desclin JC. Histological evidence supporting the inferior olive as the major source of cerebellar climbing fibers in the rat. Brain Res. 1974;77:365–84.PubMedCrossRefGoogle Scholar
  195. 195.
    Ito M. Experimental verification of Marr-Albus’ plasticity assumption for the cerebellum. Acta Biol Acad Sci Hung. 1982;33:189–99.PubMedGoogle Scholar
  196. 196.
    Ivry RB, Spencer RM, Zelaznik HN, Diedrichsen J. The cerebellum and event timing. Ann N Y Acad Sci. 2002;978:302–17.PubMedCrossRefGoogle Scholar
  197. 197.
    Lamarre Y, Chapman CE. Comparative timing of neuronal discharge in cortical and cerebellar structures during a simple arm movement in the monkey. Exp Brain Res Ser. 1986;15:14–27.Google Scholar
  198. 198.
    Llinás R. Eighteenth Bowditch lecture. Motor aspects of cerebellar control. Physiologist. 1974;17:19–46.PubMedGoogle Scholar
  199. 199.
    Mano Y, Funakawa I, Nakamuro T, Takayanagi T, Matsui K. The kinesiological, chemical and pathological analysis in pulsed magnetic stimulation to the brain. Rinsho Shinkeigaku. 1989;29:982–8.PubMedGoogle Scholar
  200. 200.
    Ito M, Kano M. Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex. Neurosci Lett. 1982;33:253–8.PubMedCrossRefGoogle Scholar
  201. 201.
    Dean P, Porrill J, Ekerot CF, Jorntell H. The cerebellar microcircuit as an adaptive filter: experimental and computational evidence. Nat Rev Neurosci. 2010;11:30–43.PubMedCrossRefGoogle Scholar
  202. 202.
    Fujita M. Simulation of adaptive modification of the vestibulo-ocular reflex with an adaptive filter model of the cerebellum. Biol Cybern. 1982;45:207–14.PubMedCrossRefGoogle Scholar
  203. 203.
    Wadiche JI, Jahr CE. Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity. Nat Neurosci. 2005;8:1329–34.PubMedCrossRefGoogle Scholar
  204. 204.
    De Zeeuw CI, Ten Brinke MM. Motor learning and the cerebellum. Cold Spring Harb Perspect Biol. 2015;7:a021683.PubMedCrossRefGoogle Scholar
  205. 205.
    De Gruijl JR, Hoogland TM, De Zeeuw CI. Behavioral correlates of complex spike synchrony in cerebellar microzones. J Neurosci. 2014;34:8937–47.PubMedCrossRefGoogle Scholar
  206. 206.
    De Gruijl JR, Sokol PA, Negrello M, De Zeeuw CI. Modulation of electrotonic coupling in the inferior olive by inhibitory and excitatory inputs: integration in the glomerulus. Neuron. 2014;81:1215–7.PubMedCrossRefGoogle Scholar
  207. 207.
    Boele HJ, Koekkoek SK, De Zeeuw CI. Cerebellar and extracerebellar involvement in mouse eyeblink conditioning: the ACDC model. Front Cell Neurosci. 2010;3:19.PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    De Zeeuw C, Koekkoek B, van Alphen A, Luo C, Hoebeek F, van Der Steen J, et al. Gain and phase control of compensatory eye movements by the flocculus of the vestibulocerebellum. The vestibular system (Handbook of auditory research) 2004. 2004:375–423.Google Scholar
  209. 209.
    De Zeeuw CI, Yeo CH. Time and tide in cerebellar memory formation. Curr Opin Neurobiol. 2005;15:667–74.PubMedCrossRefGoogle Scholar
  210. 210.
    Ito M. Synaptic plasticity in the cerebellar cortex and its role in motor learning. Can J Neurol Sci. 1993;20 Suppl 3:S70–4.PubMedGoogle Scholar
  211. 211.
    Jirenhed D-A, Hesslow G. Learning stimulus intervals—adaptive timing of conditioned Purkinje cell responses. Cerebellum. 2011;10:523–35.PubMedCrossRefGoogle Scholar
  212. 212.
    Rambold H, Churchland A, Selig Y, Jasmin L, Lisberger SG. Partial ablations of the flocculus and ventral paraflocculus in monkeys cause linked deficits in smooth pursuit eye movements and adaptive modification of the VOR. J Neurophysiol. 2002;87:912–24.PubMedPubMedCentralGoogle Scholar
  213. 213.
    Mostofi A, Holtzman T, Grout AS, Yeo CH, Edgley SA. Electrophysiological localization of eyeblink-related microzones in rabbit cerebellar cortex. J Neurosci. 2010;30:8920–34.PubMedCrossRefGoogle Scholar
  214. 214.
    Ten Brinke MM, Boele HJ, Spanke JK, Potters JW, Kornysheva K, Wulff P, et al. Evolving models of Pavlovian conditioning: cerebellar cortical dynamics in awake behaving mice. Cell Rep. 2015;13:1977–88.PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Badura A, Schonewille M, Voges K, Galliano E, Renier N, Gao Z, et al. Climbing fiber input shapes reciprocity of Purkinje cell firing. Neuron. 2013;78:700–13.PubMedCrossRefGoogle Scholar
  216. 216.
    Coesmans M, Weber JT, De Zeeuw CI, Hansel C. Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron. 2004;44:691–700.PubMedCrossRefGoogle Scholar
  217. 217.
    Piochon C, Kruskal P, Maclean J, Hansel C. Non-Hebbian spike-timing-dependent plasticity in cerebellar circuits. Front Neural Circuits. 2012;6:124.PubMedGoogle Scholar
  218. 218.
    Yang Y, Lisberger SG. Role of plasticity at different sites across the time course of cerebellar motor learning. J Neurosci. 2014;34:7077–90.PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Kistler WM, De Zeeuw CI. Dynamical working memory and timed responses: the role of reverberating loops in the olivo-cerebellar system. Neural Comput. 2002;14:2597–626.PubMedCrossRefGoogle Scholar
  220. 220.
    Welsh JP. Functional significance of climbing-fiber synchrony: a population coding and behavioral analysis. Ann N Y Acad Sci. 2002;978:188–204.PubMedCrossRefGoogle Scholar
  221. 221.
    Mathy A, Clark BA, Hausser M. Synaptically induced long-term modulation of electrical coupling in the inferior olive. Neuron. 2014;81:1290–6.PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    De Zeeuw CI, Wentzel P, Mugnaini E. Fine structure of the dorsal cap of the inferior olive and its GABAergic and non-GABAergic input from the nucleus prepositus hypoglossi in rat and rabbit. J Comp Neurol. 1993;327:63–82.PubMedCrossRefGoogle Scholar
  223. 223.
    De Zeeuw CI, Wylie DR, Stahl JS, Simpson JI. Phase relations of Purkinje cells in the rabbit flocculus during compensatory eye movements. J Neurophysiol. 1995;74:2051–64.PubMedGoogle Scholar
  224. 224.
    Bazzigaluppi P, De Gruijl JR, van der Giessen RS, Khosrovani S, De Zeeuw CI, de Jeu MT. Olivary subthreshold oscillations and burst activity revisited. Front Neural Circuits. 2012;6:91.PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Bazzigaluppi P, Ruigrok T, Saisan P, De Zeeuw CI, de Jeu M. Properties of the nucleo-olivary pathway: an in vivo whole-cell patch clamp study. PLoS One. 2012;7, e46360.PubMedPubMedCentralCrossRefGoogle Scholar
  226. 226.
    Boele HJ, Koekkoek SK, De Zeeuw CI, Ruigrok TJ. Axonal sprouting and formation of terminals in the adult cerebellum during associative motor learning. J Neurosci. 2013;33:17897–907.PubMedCrossRefGoogle Scholar
  227. 227.
    Winkelman BH, Belton T, Suh M, Coesmans M, Morpurgo MM, Simpson JI. Nonvisual complex spike signals in the rabbit cerebellar flocculus. J Neurosci. 2014;34:3218–30.PubMedPubMedCentralCrossRefGoogle Scholar
  228. 228.
    De Zeeuw CI, Hoebeek FE, Bosman LWJ, Schonewille M, Witter L, Koekkoek SK. Spatiotemporal firing patterns in the cerebellum. Nat Rev Neurosci. 2011;12:327–44.PubMedCrossRefGoogle Scholar
  229. 229.
    Person AL, Raman IM. Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei. Nature. 2011;481:502–5.PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Zhang W, Linden DJ. The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat Rev Neurosci. 2003;4:885–900.PubMedCrossRefGoogle Scholar
  231. 231.
    Bagnall MW, du Lac S. A new locus for synaptic plasticity in cerebellar circuits. Neuron. 2006;51:5–7.PubMedCrossRefGoogle Scholar
  232. 232.
    Voogd J, Schraa-Tam CK, van der Geest JN, De Zeeuw CI. Visuomotor cerebellum in human and nonhuman primates. Cerebellum. 2012;11:392–410.PubMedCrossRefGoogle Scholar
  233. 233.
    Vinueza Veloz MF, Zhou K, Bosman LW, Potters JW, Negrello M, Seepers RM, et al. Cerebellar control of gait and interlimb coordination. Brain Struct Funct. 2014.Google Scholar
  234. 234.
    Nieuwenhuys R, Puelles L. Towards a new neuromorphology. Heidelberg: Springer; 2016.CrossRefGoogle Scholar
  235. 235.
    Devor A. Is the cerebellum like cerebellar-like structures? Brain Res Brain Res Rev. 2000;34:149–56.PubMedCrossRefGoogle Scholar
  236. 236.
    Farris SM, Schulmeister S. Parasitoidism, not sociality, is associated with the evolution of elaborate mushroom bodies in the brains of hymenopteran insects. Proc Biol Sci. 2011;278:940–51.PubMedCrossRefGoogle Scholar
  237. 237.
    Hashimoto M, Hibi M. Development and evolution of cerebellar neural circuits. Dev Growth Differ. 2012;54:373–89.PubMedCrossRefGoogle Scholar
  238. 238.
    Buzsaki G, Moser EI. Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nat Neurosci. 2013;16:130–8.PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Granit R, Phillips CG. Excitatory and inhibitory processes acting upon individual Purkinje cells of the cerebellum in cats. J Physiol Lond. 1956;133:520–47.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Bell CC, Grimm RJ. Discharge properties of Purkinje cells recorded on single and double microelectrodes. J Neurophysiol. 1969;32:1044–55.PubMedGoogle Scholar
  241. 241.
    Murphy JT, Sabah NH. The inhibitory effect of climbing fiber activation on cerebellar purkinje cells. Brain Res. 1970;19:486–90.PubMedCrossRefGoogle Scholar
  242. 242.
    Latham A, Paul DH. Spontaneous activity of cerebellar Purkinje cells and their responses to impulses in climbing fibres. J Physiol Lond. 1971;213:135–56.PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Burg D, Rubia FJ. Inhibition of cerebellar Purkinje cells by climbing fiber input. Pflugers Arch. 1972;337:367–72.PubMedCrossRefGoogle Scholar
  244. 244.
    Bloedel JR, Roberts WJ. Action of climbing fibers in cerebellar cortex of the cat. J Neurophysiol. 1971;34:17–31.PubMedGoogle Scholar
  245. 245.
    Bloedel JR, Ebner TJ, Yu Q. Increased responsiveness of Purkinje cells associated with climbing fiber inputs to neighboring neurons. J Neurophysiol. 1983;50:220–39.PubMedGoogle Scholar
  246. 246.
    Ebner TJ, Bloedel JR. Temporal patterning in simple spike discharge of Purkinje cells and Its relationship to climbing fiber activity. J Neurophysiol. 1981;45:933–47.PubMedGoogle Scholar
  247. 247.
    Ebner TJ, Bloedel JR. Role of climbing fiber afferent input in determining responsiveness of Purkinje cells to mossy fiber inputs. J Neurophysiol. 1981;45:962–71.PubMedGoogle Scholar
  248. 248.
    Ebner TJ, Yu Q, Bloedel JR. Increase in Purkinje cell gain associated with naturally activated climbing fiber input. J Neurophysiol. 1983;50:205–19.PubMedGoogle Scholar
  249. 249.
    Mano N, Kanazawa I, Yamamoto K. Complex-spike activity of cerebellar Purkinje cells related to wrist tracking movement in monkey. J Neurophysiol. 1986;56:137–58.PubMedGoogle Scholar
  250. 250.
    Sato Y, Miura A, Fushiki H, Kawasaki T. Short-term modulation of cerebellar Purkinje cell activity after spontaneous climbing fiber input. J Neurophysiol. 1992;68:2051–62.PubMedGoogle Scholar
  251. 251.
    Miall RC, Keating JG, Malkmus M, Thach WT. Simple spike activity predicts occurrence of complex spikes in cerebellar Purkinje cells. Nat Neurosci. 1998;1:13–5.PubMedCrossRefGoogle Scholar
  252. 252.
    Montarolo PG, Palestini M, Strata P. The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat. J Physiol Lond. 1982;332:187–202.PubMedPubMedCentralCrossRefGoogle Scholar
  253. 253.
    Rawson JA, Tilokskulchai K. Suppression of simple spike discharges of cerebellar Purkinje cells by impulses in climbing fibre afferents. Neurosci Lett. 1981;25:125–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Eric J. Lang
    • 1
  • Richard Apps
    • 2
  • Fredrik Bengtsson
    • 3
  • Nadia L Cerminara
    • 2
  • Chris I De Zeeuw
    • 4
    • 5
  • Timothy J. Ebner
    • 6
  • Detlef H. Heck
    • 7
  • Dieter Jaeger
    • 8
  • Henrik Jörntell
    • 3
  • Mitsuo Kawato
    • 9
  • Thomas S. Otis
    • 10
  • Ozgecan Ozyildirim
    • 5
  • Laurentiu S. Popa
    • 6
  • Alexander M. B. Reeves
    • 10
  • Nicolas Schweighofer
    • 11
  • Izumi Sugihara
    • 12
  • Jianqiang Xiao
    • 1
  1. 1.Department of Neuroscience and PhysiologyNew York University School of MedicineNew YorkUSA
  2. 2.School of Physiology, Pharmacology and NeuroscienceUniversity of BristolBristolUK
  3. 3.Neural Basis for Sensorimotor Control, Department of Experimental Medical ScienceLund UniversityLundSweden
  4. 4.Department of NeuroscienceErasmus MC RotterdamRotterdamThe Netherlands
  5. 5.Netherlands Institute for NeuroscienceRoyal Netherlands Academy of Arts and SciencesAmsterdamThe Netherlands
  6. 6.Department of NeuroscienceUniversity of MinnesotaMinneapolisUSA
  7. 7.Department Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  8. 8.Department of BiologyEmory UniversityAtlantaUSA
  9. 9.Brain Information Communication Research Laboratory GroupATRKyotoJapan
  10. 10.Department of Neurobiology and Integrated Center for Learning and MemoryGeffen School of Medicine at UCLALos AngelesUSA
  11. 11.Division of Biokinesiology and Physical TherapyUniversity of Southern CaliforniaLos AngelesUSA
  12. 12.Department of Systems Neurophysiology, Graduate School of Medical and Dental Sciences, and Center for Brain Integration ResearchTokyo Medical and Dental UniversityTokyoJapan

Personalised recommendations