Advertisement

Cerebellar Nuclei and Cerebellar Learning

  • Dieter JaegerEmail author
Living reference work entry

Abstract

The cerebellar nuclei (CN) and the vestibular nucleus are the only recipients of output from the cerebellar cortex and provide the only final output pathway of cerebellar processing. This cortico-nuclear pathway is mediated entirely by GABA inhibition via Purkinje cell (PC) axons, yet conveys important information regarding the fine temporal control of behavior. Therefore, the interesting question arises of how one can control finely tuned CN output spike patterns with inhibition, challenging our understanding of neural coding. Using the technique of dynamic clamp, artificial inhibitory synaptic input patterns can be applied to CN neurons to explore this question. It was found that a population code in which a set of PCs pause at the same time creates an efficient code to precisely trigger individual CN spikes via disinhibition. Strong inhibition can paradoxically also evoke spiking, namely, by a mechanism of postinhibitory rebound, a pronounced property of CN neurons. Strong bursts of PC activity followed by pauses of firing create an ideal stimulus for rebound generation and are elicited by synchronous climbing fiber inputs to cerebellar cortex. Such a stimulus-evoked rebound could trigger specific behavioral responses, though direct evidence for this mechanism is currently lacking. Finally, there are also strong data and modeling results to support a traditional rate coding concepts in the PC to CN connection, which allows for an analog modulation of spike rate in the CN based on equally analog up-and-down modulation of PC spike rates in the opposite direction. These different coding principles are likely to operate in parallel and be important under different behavioral contexts.

The conditioned eyeblink reflex in particular has been extensively studied with respect to learning mechanisms in the CN. Activity in the CN develops an increase just before the eyeblink during learning, and this CN activation depends on plasticity in the excitatory input to CN neurons by mossy fibers. Interestingly, this form of plasticity has been first predicted and then found to be controlled by the activity of inhibitory PC input. The cellular basis for this form of plasticity ultimately depends on a complex set of calcium signaling events during inputs in the required sequence of MF inputs followed by inhibition, followed by repolarization. A similar mechanism is proposed to also underlie the adaptation of vestibulo-ocular gain control coded by the vestibular nuclei. The involvement of similar or different learning mechanisms in the CN in more complex limb movement control remains to be determined, but behavioral and electrophysiological evidence points in the direction that the precise timing of predictive submovement activation in coordinated limb movements may be the predominant function of cerebellar output from the CN in this regard.

Keywords

Calcium Cerebellar nuclei Climbing fiber Conditioned stimulus Cortico-nuclear module Cross-modal transfer Delay conditioning Dynamic clamp Extinction Eyeblink conditioning GABA Glutamate Hebbian Hyperpolarization Inferior olive Inhibition Interpositus nucleus Learning Long-term depression (LTD) Long-term potentiation (LTP) Microzone Mossy fiber Motor learning Optogenetics Pause Persistent sodium current Plasticity Postinhibitory rebound Purkinje cells Rebound burst Short-latency response Short-term depression Spontaneous spiking Structural plasticity Synapse specific Theta Timing Tonic firing Trace conditioning T-type calcium channel Unconditioned stimulus Vestibular nucleus Vestibulo-ocular reflex (VOR) VOR 

References

  1. Abbasi S, Hudson AE, Maran SK, Cao Y, Abbasi A, Heck DH, Jaeger D (2017) Robust transmission of rate coding in the inhibitory Purkinje cell to cerebellar nuclei pathway in awake mice. PLoS Comput Biol 13:e1005578PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aizenman CD, Linden DJ (1999) Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum. J Neurophysiol 82:1697–1709CrossRefGoogle Scholar
  3. Aizenman CD, Linden DJ (2000) Rapid, synaptically driven increases in the intrinsic excitability of cerebellar deep nuclear neurons. Nat Neurosci 3:109–111PubMedCrossRefPubMedCentralGoogle Scholar
  4. Aizenman CD, Manis PB, Linden DJ (1998) Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron 21:827–835Google Scholar
  5. Albus JS (1971) A theory of cerebellar function. Math Biosci 10:25–61Google Scholar
  6. Alvina K, Walter JT, Kohn A, Ellis-Davies G, Khodakhah K (2008) Questioning the role of rebound firing in the cerebellum. Nat Neurosci 11:1256–1258PubMedPubMedCentralCrossRefGoogle Scholar
  7. Angaut P, Sotelo C (1989) Synaptology of the cerebello-olivary pathway. Double labelling with anterograde axonal tracing and GABA immunocytochemistry in the rat. Brain Res 479:361–365PubMedCrossRefPubMedCentralGoogle Scholar
  8. Ankri L, Husson Z, Pietrajtis K, Proville R, Léna C, Yarom Y, Dieudonné S, Uusisaari MY (2015) A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity. elife 4:e06262Google Scholar
  9. Armstrong DM, Edgley SA (1984) Discharges of nucleus interpositus neurones during locomotion in the cat. J Physiol 351:411–432PubMedPubMedCentralCrossRefGoogle Scholar
  10. Armstrong DM, Rawson JA (1979) Responses of neurones in nucleus interpositus of the cerebellum to cutaneous nerve volleys in the awake cat. J Physiol 289:403–423PubMedPubMedCentralCrossRefGoogle Scholar
  11. Armstrong DM, Cogdell B, Harvey R (1975) Effects of afferent volleys from the limbs on the discharge patterns of interpositus neurones in cats anaesthetized with alpha-chloralose. J Physiol 248:489–517PubMedPubMedCentralCrossRefGoogle Scholar
  12. Beck H, Yaari Y (2008) Plasticity of intrinsic neuronal properties in CNS disorders. Nat Rev Neurosci 9:357–369PubMedCrossRefPubMedCentralGoogle Scholar
  13. Beitzel CS, Houck BD, Lewis SM, Person AL (2017) Rubrocerebellar feedback loop isolates the interposed nucleus as an independent processor of corollary discharge information in mice. J Neurosci 37:10085PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bengtsson F, Ekerot CF, Jorntell H (2011) In vivo analysis of inhibitory synaptic inputs and rebounds in deep cerebellar nuclear neurons. PLoS One 6:e18822PubMedPubMedCentralCrossRefGoogle Scholar
  15. Berry SD, Hoffmann LC (2011) Hippocampal theta-dependent eyeblink classical conditioning: coordination of a distributed learning system. Neurobiol Learn Mem 95:185–189PubMedCrossRefPubMedCentralGoogle Scholar
  16. Boele HJ, Koekkoek SKE, De Zeeuw CI (2010) Cerebellar and extracerebellar involvement in mouse eyeblink conditioning: the ACDC model. Front Cell Neurosci 3:19Google Scholar
  17. Boyden ES, Katoh A, Raymond JL (2004) Cerebellum-dependent learning: the role of multiple plasticity mechanisms. Annu Rev Neurosci 27:581–609PubMedCrossRefPubMedCentralGoogle Scholar
  18. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268PubMedPubMedCentralCrossRefGoogle Scholar
  19. Braitenberg V (1967) Is the cerebellar cortex a biological clock in the millisecond range? Prog Brain Res 25:334–346PubMedCrossRefPubMedCentralGoogle Scholar
  20. Broussard DM, Lisberger SG (1992) Vestibular inputs to brain stem neurons that participate in motor learning in the primate vestibuloocular reflex. J Neurophysiol 68:1906–1909PubMedCrossRefPubMedCentralGoogle Scholar
  21. Burguiere E, Arabo A, Jarlier F, De Zeeuw CI, Rondi-Reig L (2010) Role of the cerebellar cortex in conditioned goal-directed behavior. J Neurosci 30:13265–13271PubMedCrossRefPubMedCentralGoogle Scholar
  22. Campolattaro MM, Kashef A, Lee I, Freeman JH (2011) Neuronal correlates of cross-modal transfer in the cerebellum and pontine nuclei. J Neurosci 31:4051–4062PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cao Y, Maran SK, Dhamala M, Jaeger D, Heck DH (2012) Behavior-related pauses in simple-spike activity of mouse Purkinje cells are linked to spike rate modulation. J Neurosci 32:8678–8685PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chan-Palay V (1973) Neuronal plasticity in cerebellar cortex and lateral nucleus. Z Anat Entwicklungsgesch 142:23–35PubMedCrossRefPubMedCentralGoogle Scholar
  25. Chan-Palay V (1977) Cerebellar dentate nucleus. Springer, Berlin/HeidelbergCrossRefGoogle Scholar
  26. Chen S, Hillman DE (1993) Colocalization of neurotransmitters in the deep cerebellar nuclei. J Neurocytol 22:81–91PubMedPubMedCentralCrossRefGoogle Scholar
  27. Christian KM, Thompson RF (2003) Neural substrates of Eyeblink conditioning: acquisition and retention. Learn Memory 10:427–455CrossRefGoogle Scholar
  28. Clopath C, Badura A, De Zeeuw CI, Brunel N (2014) A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice. J Neurosci 34:7203–7215PubMedCrossRefPubMedCentralGoogle Scholar
  29. Cooper SE, Martin JH, Ghez C (2000) Effects of inactivation of the anterior interpositus nucleus on the kinematic and dynamic control of multijoint movement. J Neurophysiol 84:1988–2000PubMedCrossRefPubMedCentralGoogle Scholar
  30. Crook S, Gleeson P, Howell F, Svitak J, Silver RA (2007) MorphML: level 1 of the NeuroML standards for neuronal morphology data and model specification. Neuroinformatics 5:96–104PubMedPubMedCentralCrossRefGoogle Scholar
  31. Crook S, Silver RA, Gleeson P (2009) Describing and exchanging models of neurons and neuronal networks with NeuroML. BMC Neurosci 10:1–2CrossRefGoogle Scholar
  32. Daoudal G, Debanne D (2003) Long-term plasticity of intrinsic excitability: learning rules and mechanisms. Learn Memory 10:456–465CrossRefGoogle Scholar
  33. De Schutter E (1995) Cerebellar long-term depression might normalize excitation of Purkinje cells. Trends Neurosci 18:291–295PubMedCrossRefPubMedCentralGoogle Scholar
  34. De Schutter E, Bower JM (1994) An active membrane model of the cerebellar Purkinje cell I. Simulation of current clamp in slice. J Neurophysiol 71:375–400PubMedCrossRefPubMedCentralGoogle Scholar
  35. De Schutter E, Steuber V (2009) Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory. Neuroscience 162:816–826PubMedCrossRefPubMedCentralGoogle Scholar
  36. De Zeeuw CI, Wylie DR, DiGiorgi PL, Simpson JI (1994) Projections of individual Purkinje cells of identified zones in the flocculus to the vestibular and cerebellar nuclei in the rabbit. J Comp Neurol 349:428–447PubMedCrossRefPubMedCentralGoogle Scholar
  37. Desai NS, Rutherford LC, Turrigiano GG (1999) Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nat Neurosci 2:515–520PubMedCrossRefPubMedCentralGoogle Scholar
  38. Ekerot CF, Jorntell H, Garwicz M (1995) Functional relation between corticonuclear input and movements evoked on microstimulation in cerebellar nucleus interpositus anterior in the cat. Exp Brain Res 106:365–376PubMedCrossRefPubMedCentralGoogle Scholar
  39. Fredette BJ, Mugnaini E (1991) The GABAergic cerebello-olivary projection in the rat. Anat Embryol (Berl) 184:225–243CrossRefGoogle Scholar
  40. Gabbiani F, Midtgaard J, Knöpfel T (1994) Synaptic integration in a model of cerebellar granule cells. JNeurophysiol 72:999–1009CrossRefGoogle Scholar
  41. Gao ZY, Proietti-Onori M, Lin ZM, ten Brinke MM, Boele HJ, Potters JW, Ruigrok TJH, Hoebeek FE, De Zeeuw CI (2016) Excitatory cerebellar Nucleocortical circuit provides internal amplification during associative conditioning. Neuron 89:645–657PubMedPubMedCentralCrossRefGoogle Scholar
  42. Garcia KS, Steele PM, Mauk MD (1999) Cerebellar cortex lesions prevent acquisition of conditioned eyelid responses. J Neurosci 19:10940–10947PubMedCrossRefPubMedCentralGoogle Scholar
  43. Gardner EP, Fuchs AF (1975) Single-unit responses to natural vestibular stimuli and eye movements in deep cerebellar nuclei of the alert rhesus monkey. J Neurophysiol 38:627–649PubMedCrossRefPubMedCentralGoogle Scholar
  44. Garwicz M, Ekerot CF (1994) Topographical organization of the cerebellar cortical projection to nucleus interpositus anterior in the cat. J Physiol 474:245–260PubMedPubMedCentralCrossRefGoogle Scholar
  45. Gauck V, Jaeger D (2000) The control of rate and timing of spikes in the deep cerebellar nuclei by inhibition. J Neurosci 20:3006–3016CrossRefGoogle Scholar
  46. Gauck V, Jaeger D (2003) The contribution of NMDA and AMPA conductances to the control of spiking in neurons of the deep cerebellar nuclei. J Neurosci 23:8109–8118PubMedCrossRefPubMedCentralGoogle Scholar
  47. Gleeson P, Steuber V, Silver RA (2007) neuroConstruct: a tool for modeling networks of neurons in 3D space. Neuron 54:219–235PubMedPubMedCentralCrossRefGoogle Scholar
  48. Gleeson P, Crook S, Cannon RC, Hines ML, Billings GO, Farinella M, Morse TM, Davison AP, Ray S, Bhalla US, Barnes SR, Dimitrova YD, Silver RA (2010) NeuroML: a language for describing data driven models of neurons and networks with a high degree of biological detail. PLoS Comput Biol 6:e1000815PubMedPubMedCentralCrossRefGoogle Scholar
  49. Goodman DC, Hallett RE, Welch RB (1963) Patterns of localization in the cerebellar corticonuclear projections of albino rat. J Comp Neurol 121:51–67PubMedCrossRefPubMedCentralGoogle Scholar
  50. Granit R, Phillips CG (1956) Excitatory and inhibitory processes acting upon individual Purkinje cells of the cerebellum of cats. J Physiol (Lond) 133:520–547CrossRefGoogle Scholar
  51. Graybiel AM, Nauta HJW, Lasek RJ, Nauta WJH (1973) Cerebello-olivary pathway in cat – experimental study using autoradiographic tracing techniques. Brain Res 58:205–211PubMedCrossRefPubMedCentralGoogle Scholar
  52. Grimm RJ, Rushmer DS (1974) The activity of dentate neurons during an arm movement sequence. Brain Res 71:309–326PubMedCrossRefPubMedCentralGoogle Scholar
  53. Harvey RJ, Porter R, Rawson JA (1979) Discharges of intracerebellar nuclear cells in monkeys. J Physiol 297:559–580PubMedPubMedCentralCrossRefGoogle Scholar
  54. Heck DH, De Zeeuw CI, Jaeger D, Khodakhah K, Person AL (2013) The neuronal code(s) of the cerebellum. J Neurosci 33:17603–17609. PMC3818542PubMedPubMedCentralCrossRefGoogle Scholar
  55. Heinen SJ, Keller EL (1996) The function of the cerebellar uvula in monkey during optokinetic and pursuit eye movements: single-unit responses and lesion effects. Exp Brain Res 110:1–14PubMedCrossRefPubMedCentralGoogle Scholar
  56. Heiney SA, Kim J, Augustine GJ, Medina JF (2014) Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity. J Neurosci 34:2321–2330PubMedPubMedCentralCrossRefGoogle Scholar
  57. Hepp K, Henn V, Jaeger J (1982) Eye movement related neurons in the cerebellar nuclei of the alert monkey. Exp Brain Res 45:253–264PubMedPubMedCentralGoogle Scholar
  58. Hoebeek FE, Witter L, Ruigrok TJ, De Zeeuw CI (2010) Differential olivo-cerebellar cortical control of rebound activity in the cerebellar nuclei. Proc Natl Acad Sci U S A 107:8410–8415. 2889566PubMedPubMedCentralCrossRefGoogle Scholar
  59. Hoffmann LC, Berry SD (2009) Cerebellar theta oscillations are synchronized during hippocampal theta-contingent trace conditioning. Proc Natl Acad Sci 106:21371–21376PubMedCrossRefPubMedCentralGoogle Scholar
  60. Holdefer RN, Houk JC, Miller LE (2005) Movement-related discharge in the cerebellar nuclei persists after local injections of GABA(a) antagonists. J Neurophysiol 93:35–43PubMedCrossRefPubMedCentralGoogle Scholar
  61. Ishikawa T, Tomatsu S, Tsunoda Y, Lee J, Hoffman DS, Kakei S (2014) Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the Cerebrocerebellum. PLoS One 9:e108774PubMedPubMedCentralCrossRefGoogle Scholar
  62. Ito M (1984) The cerebellum and neural control. Raven Press, New YorkGoogle Scholar
  63. Ito M (1993) Cerebellar flocculus hypothesis. Nature 363:24–25PubMedCrossRefPubMedCentralGoogle Scholar
  64. Ito M (2001) Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195PubMedCrossRefPubMedCentralGoogle Scholar
  65. Ito M, Kano M (1982) 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 33:253–258PubMedCrossRefPubMedCentralGoogle Scholar
  66. Ivry RB (1996) The representation of temporal information in perception and motor control. [review] [51 refs]. Curr Opin Neurobiol 6:851–857PubMedCrossRefPubMedCentralGoogle Scholar
  67. Ivry RB, Spencer RMC (2004) The neural representation of time. Curr Opin Neurobiol 14:225–232PubMedCrossRefPubMedCentralGoogle Scholar
  68. Jaeger D, Jorntell H, Kawato M (2013) Computation in the cerebellum. Neural Netw Off J Int Neural Netw Soc 47:1–2CrossRefGoogle Scholar
  69. Jahnsen H (1986a) Extracellular activation and membrane conductances of neurones in the Guinea-pig deep cerebellar nuclei in vitro. J Physiol 372:149–168PubMedPubMedCentralCrossRefGoogle Scholar
  70. Jahnsen H (1986b) Electrophysiological characteristics of neurones in the Guinea-pig deep cerebellar nuclei in vitro. J Physiol 372:129–147PubMedPubMedCentralCrossRefGoogle Scholar
  71. Jansen J (1955) On the efferent fibers of the cerebellar nuclei in the cat. J Comp Neurol 102:607–632PubMedCrossRefPubMedCentralGoogle Scholar
  72. Lisberger SG (1988) The neural basis for learning of simple motor skills. Science 242:728–735PubMedCrossRefPubMedCentralGoogle Scholar
  73. Lisberger SG (1994) Neural basis for motor learning in the vestibuloocular reflex of primates. III. Computational and behavioral analysis of the sites of learning. J Neurophysiol 72:974–998PubMedCrossRefPubMedCentralGoogle Scholar
  74. Lisberger SG, Pavelko TA, Broussard DM (1994a) Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons. J Neurophysiol 72:928–953PubMedCrossRefPubMedCentralGoogle Scholar
  75. Lisberger SG, Pavelko TA, Bronte-Stewart HM, Stone LS (1994b) Neural basis for motor learning in the vestibuloocular reflex of primates. II. Changes in the responses of horizontal gaze velocity Purkinje cells in the cerebellar flocculus and ventral paraflocculus. J Neurophysiol 72:954–973PubMedCrossRefPubMedCentralGoogle Scholar
  76. Llinas R, Muhlethaler M (1988) Electrophysiology of Guinea-pig cerebellar nuclear cells in the in vitro brain stem-cerebellar preparation. J Physiol 404:241–258PubMedPubMedCentralCrossRefGoogle Scholar
  77. Luque NR, Garrido JA, Naveros F, Carrillo RR, D'Angelo E, Ros E (2016) Distributed cerebellar motor learning: a spike-timing-dependent plasticity model. Front Comput Neurosci 10:17Google Scholar
  78. Maex R, De Schutter E (2005) Oscillations in the cerebellar cortex: a prediction of their frequency bands. Prog Brain Res 148:181–188PubMedCrossRefPubMedCentralGoogle Scholar
  79. Marr D (1969) A theory of cerebellar cortex. J Physiol Lond 202:437–470PubMedPubMedCentralCrossRefGoogle Scholar
  80. Matsushita M, Iwahori N (1971a) Structural organization of the fastigial nucleus. I. Dendrites and axonal pathways. Brain Res 25:597–610PubMedCrossRefPubMedCentralGoogle Scholar
  81. Matsushita M, Iwahori N (1971b) Structural organization of the interpositus and the dentate nuclei. Brain Res 35:17–36PubMedCrossRefPubMedCentralGoogle Scholar
  82. Mauk MD (1997) Roles of cerebellar cortex and nuclei in motor learning: contradictions or clues? Neuron 18:343–346PubMedCrossRefPubMedCentralGoogle Scholar
  83. McCormick DA, Thompson RF (1984) Neuronal responses of the rabbit cerebellum during acquisition and PERFORMANCE of a classically-conditioned nictitating membrane-eyelid response. J Neurosci 4:2811–2822CrossRefGoogle Scholar
  84. McCormick DA, Lavond DG, Clark GA, Kettner RE, Rising CE, Thompson RF (1981) The engram found questionable role of the cerebellum in classical-conditioning of nictitating-membrane and eyelid responses. Bull Psychon Soc 18:103–105CrossRefGoogle Scholar
  85. McCormick DA, Clark GA, Lavond DG, Thompson RF (1982) Initial localization of the memory trace for a basic form of learning. Proc Natl Acad Sci U S A – Biol Sci 79:2731–2735CrossRefGoogle Scholar
  86. Medina JF, Mauk MD (1999) Simulations of cerebellar motor learning: computational analysis of plasticity at the mossy fiber to deep nucleus synapse. J Neurosci 19:7140–7151PubMedCrossRefPubMedCentralGoogle Scholar
  87. Medina JF, Garcia KS, Nores WL, Taylor NM, Mauk MD (2000) Timing mechanisms in the cerebellum: testing predictions of a large-scale computer simulation. J Neurosci 20:5516–5525PubMedCrossRefPubMedCentralGoogle Scholar
  88. Medina JF, Garcia KS, Mauk MD (2001) A mechanism for savings in the cerebellum. J Neurosci 21:4081–4089PubMedCrossRefPubMedCentralGoogle Scholar
  89. Milak MS, Bracha V, Bloedel JR (1995) Relationship of simultaneously recorded cerebellar nuclear neuron discharge to the acquisition of a complex, operantly conditioned forelimb movement in cats. Exp Brain Res 105:325–330PubMedCrossRefPubMedCentralGoogle Scholar
  90. Milak MS, Shimansky Y, Bracha V, Bloedel JR (1997) Effects of inactivating individual cerebellar nuclei on the Performance and retention of an Operantly conditioned forelimb movement. J Neurophysiol 78:939–959PubMedCrossRefPubMedCentralGoogle Scholar
  91. Miles FA, Lisberger SG (1981) Plasticity in the vestibulo-ocular reflex: a new hypothesis. Annu Rev Neurosci 4:273–299PubMedCrossRefPubMedCentralGoogle Scholar
  92. Molineux ML, McRory JE, McKay BE, Hamid J, Mehaffey WH, Rehak R, Snutch TP, Zamponi GW, Turner RW (2006) Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. Proc Natl Acad Sci U S A 103:5555–5560PubMedPubMedCentralCrossRefGoogle Scholar
  93. Molineux ML, Mehaffey WH, Tadayonnejad R, Anderson D, Tennent AF, Turner RW (2008) Ionic factors governing rebound burst phenotype in rat deep cerebellar neurons. J Neurophysiol 100:2684–2701PubMedCrossRefPubMedCentralGoogle Scholar
  94. Morishita W, Sastry BR (1996) Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei. J Neurophysiol 76:59–68PubMedCrossRefPubMedCentralGoogle Scholar
  95. Nagao S, Honda T, Yamazaki T (2013) Transfer of memory trace of cerebellum-dependent motor learning in human prism adaptation: a model study. Neural Netw 47:72–80PubMedCrossRefPubMedCentralGoogle Scholar
  96. Najac M, Raman IM (2015) Integration of Purkinje cell inhibition by cerebellar Nucleo-Olivary neurons. J Neurosci 35:544–549PubMedPubMedCentralCrossRefGoogle Scholar
  97. Nelson AB, Krispel CM, Sekirnjak C, du Lac S (2003) Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40:609–620PubMedCrossRefPubMedCentralGoogle Scholar
  98. Ohtsuka K, Noda H (1991) Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys. J Neurophysiol 65:1422–1434PubMedCrossRefPubMedCentralGoogle Scholar
  99. Ohyama T, Nores WL, Mauk MD (2003) Stimulus generalization of conditioned eyelid responses produced without cerebellar cortex: implications for plasticity in the cerebellar nuclei. Learn Memory 10:346–354CrossRefGoogle Scholar
  100. Ohyama T, Nores WL, Medina JF, Riusech FA, Mauk MD (2006) Learning-induced plasticity in deep cerebellar nucleus. J Neurosci 26:12656–12663PubMedCrossRefPubMedCentralGoogle Scholar
  101. Palkovits M, Mezey E, Hamori J, Szentagothai J (1977) Quantitative histological analysis of the cerebellar nuclei in the cat. I. Numerical data on cells and synapses. Exp Brain Res 28:189–209PubMedPubMedCentralGoogle Scholar
  102. Pedroarena CM, Schwarz C (2003) Efficacy and short-term plasticity at GABAergic synapses between Purkinje and cerebellar nuclei neurons. J Neurophysiol 89:704–715PubMedCrossRefPubMedCentralGoogle Scholar
  103. Pellionisz A, Llinás R (1977) A computer model of cerebellar Purkinje cells. Neuroscience 2:37–48PubMedCrossRefPubMedCentralGoogle Scholar
  104. Pellionisz A, Llinás R (1979) Brain modeling by tensor network theory and computer simulation. The cerebellum: distributed processor for predictive coordination. Neuroscience 4:323–348PubMedCrossRefPubMedCentralGoogle Scholar
  105. Pellionisz A, Szentagothai J (1974) Dynamic single unit simulation of a realistic cerebellar network model. II. Purkinje cell activity within the basic circuit and modified by inhibitory systems. Brain Res 68:19–40PubMedCrossRefPubMedCentralGoogle Scholar
  106. Perciavalle V, Apps R, Bracha V, Delgado-Garcia JM, Gibson AR, Leggio M, Carrel AJ, Cerminara N, Coco M, Gruart A, Sanchez-Campusano R (2013) Consensus paper: current views on the role of cerebellar interpositus nucleus in movement control and emotion. Cerebellum 12:738–757PubMedCrossRefPubMedCentralGoogle Scholar
  107. Perrett SP, Mauk MD (1995) Extinction of conditioned eyelid responses requires the anterior lobe of cerebellar cortex. J Neurosci 15:2074–2080PubMedCrossRefPubMedCentralGoogle Scholar
  108. Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13:1708–1718PubMedCrossRefPubMedCentralGoogle Scholar
  109. Person AL, Raman IM (2010) Deactivation of L-type ca current by inhibition controls LTP at excitatory synapses in the cerebellar nuclei. Neuron 66:550–559PubMedPubMedCentralCrossRefGoogle Scholar
  110. Person AL, Raman IM (2012) Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei. Nature 481:502–506CrossRefGoogle Scholar
  111. Pugh JR, Raman IM (2006) Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current. Neuron 51:113–123CrossRefGoogle Scholar
  112. Pugh JR, Raman IM (2008) Mechanisms of potentiation of mossy Fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition. J Neurosci 28:10549–10560PubMedPubMedCentralCrossRefGoogle Scholar
  113. Racine RJ, Wilson DA, Gingell R, Sunderland D (1986) Long-term potentiation in the interpositus and vestibular nuclei in the rat. Exp Brain Res 63:158–162PubMedCrossRefPubMedCentralGoogle Scholar
  114. Ramachandran R, Lisberger SG (2008) Neural substrate of modified and unmodified pathways for learning in monkey vestibuloocular reflex. J Neurophysiol 100:1868–1878.2576200PubMedPubMedCentralCrossRefGoogle Scholar
  115. Raman IM, Gustafson AE, Padgett D (2000) Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci 20:9004–9016PubMedCrossRefPubMedCentralGoogle Scholar
  116. Raymond JL, Lisberger SG, Mauk MD (1996) The cerebellum: a neuronal learning machine? Science 272:1126–1131PubMedCrossRefPubMedCentralGoogle Scholar
  117. Robinson HPC, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Methods 49:157–165PubMedCrossRefPubMedCentralGoogle Scholar
  118. Rowland NC, Jaeger D (2005) Coding of tactile response properties in the rat deep cerebellar nuclei. J Neurophysiol 94:1236–1251PubMedCrossRefPubMedCentralGoogle Scholar
  119. Rowland NC, Jaeger D (2008) Responses to tactile stimulation in deep cerebellar nucleus neurons result from recurrent activation in multiple pathways. J Neurophysiol 99:704–717PubMedCrossRefPubMedCentralGoogle Scholar
  120. Sangrey T, Jaeger D (2010) Multiple components of rebound spiking in deep cerebellar nucleus neurons. Eur J Neurosci 32:1646–1657PubMedPubMedCentralCrossRefGoogle Scholar
  121. Sato Y, Miura A, Fushiki H, Kawasaki T (1992) Short-term modulation of cerebellar purkinje-cell activity after spontaneous climbing fiber input. J Neurophysiol 68:2051–2062PubMedCrossRefPubMedCentralGoogle Scholar
  122. Shaikh AG, Ghasia FF, Dickman JD, Angelaki DE (2005) Properties of cerebellar fastigial neurons during translation, rotation, and eye movements. J Neurophysiol 93:853–863PubMedCrossRefPubMedCentralGoogle Scholar
  123. Sharp AA, Oneil MB, Abbott LF, Marder E (1993) Dynamic clamp – computer-generated Conductances in real neurons. J Neurophysiol 69:992–995PubMedCrossRefPubMedCentralGoogle Scholar
  124. Shin SL, De Schutter E (2006) Dynamic synchronization of Purkinje cell simple spikes. J Neurophysiol 96:3485–3491CrossRefGoogle Scholar
  125. Sjostrom PJ, Rancz EA, Roth A, Hausser M (2008) Dendritic excitability and synaptic plasticity. Physiol Rev 88:769–840PubMedCrossRefPubMedCentralGoogle Scholar
  126. Solinas S, Forti L, Cesana E, Mapelli J, De Schutter E, D'Angelo E (2007) Computational reconstruction of pacemaking and intrinsic electroresponsiveness in cerebellar Golgi cells. Front Cell Neurosci 1:2PubMedPubMedCentralCrossRefGoogle Scholar
  127. Solinas S, Nieus T, D'Angelo E (2010) A realistic large-scale model of the cerebellum granular layer predicts circuit spatio-temporal filtering properties. Front Cell Neurosci 4:12Google Scholar
  128. Steuber V, Schultheiss NW, Silver RA, De Schutter E, Jaeger D (2011) Determinants of synaptic integration and heterogeneity in rebound firing explored with data driven models of deep cerebellar nucleus cells. J Comput Neurosci 30:633–658PubMedCrossRefPubMedCentralGoogle Scholar
  129. Sudhakar SK, Torben-Nielsen B, De Schutter E (2015) Cerebellar nuclear neurons use time and rate coding to transmit Purkinje neuron pauses. PLoS Comput Biol 11:e1004641. Pmc4668013PubMedPubMedCentralCrossRefGoogle Scholar
  130. Tadayonnejad R, Anderson D, Molineux M, Mehaffey W, Jayasuriya K, Turner R (2010) Rebound discharge in deep cerebellar nuclear neurons in vitro. Cerebellum 9:352–374PubMedPubMedCentralCrossRefGoogle Scholar
  131. Telgkamp P, Raman IM (2002) Depression of inhibitory synaptic transmission between Purkinje cells and neurons of the cerebellar nuclei. J Neurosci 22:8447–8457PubMedCrossRefPubMedCentralGoogle Scholar
  132. ten Brinke MM, Heiney SA, Wang XL, Proietti-Onori M, Boele HJ, Bakermans J, Medina JF, Gao Z, De Zeeuw CI (2017) Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice. elife 6:e28132Google Scholar
  133. Teune TM, van der Burg J, de Zeeuw CI, Voogd J, Ruigrok TJ (1998) Single Purkinje cell can innervate multiple classes of projection neurons in the cerebellar nuclei of the rat: a light microscopic and ultrastructural triple-tracer study in the rat. J Comp Neurol 392:164–178PubMedPubMedCentralCrossRefGoogle Scholar
  134. Thompson RF, Steinmetz JE (2009) The role of the cerebellum in classical conditioning of discrete behavioral responses. Neuroscience 162:732–755PubMedCrossRefPubMedCentralGoogle Scholar
  135. Turecek J, Jackman SL, Regehr WG (2016) Synaptic specializations support frequency-independent Purkinje cell output from the cerebellar cortex. Cell Rep 17:3256–3268PubMedPubMedCentralCrossRefGoogle Scholar
  136. Uusisaari M, De Schutter E (2011) The mysterious microcircuitry of the cerebellar nuclei. J Physiol 589:3441–3457PubMedPubMedCentralCrossRefGoogle Scholar
  137. Uusisaari MY, Knopfel T (2012) Diversity of neuronal elements and circuitry in the cerebellar nuclei. Cerebellum 11:420–421PubMedCrossRefPubMedCentralGoogle Scholar
  138. Uusisaari M, Obata K, Knopfel T (2007) Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei. J Neurophysiol 97:901–911PubMedCrossRefPubMedCentralGoogle Scholar
  139. van Kan PLE, Horn KM, Gibson AR (1994) The importance of hand use to discharge of interpositus neurons of the monkey. J Physiol-Lond 480:171–190PubMedPubMedCentralCrossRefGoogle Scholar
  140. Walter JT, Khodakhah K (2009) The advantages of linear information processing for cerebellar computation. Proc Natl Acad Sci U S A 106:4471–4476PubMedCrossRefPubMedCentralGoogle Scholar
  141. Wang JJ, Shimansky Y, Bracha V, Bloedel JR (1998) Effects of cerebellar nuclear inactivation on the learning of a complex forelimb movement in cats. J Neurophysiol 79:2447–2459PubMedCrossRefPubMedCentralGoogle Scholar
  142. Wetmore DZ, Mukamel EA, Schnitzer MJ (2008) Lock-and-key mechanisms of cerebellar memory recall based on rebound currents. J Neurophysiol 100:2328–2347PubMedCrossRefPubMedCentralGoogle Scholar
  143. Witter L, Canto CB, Hoogland TM, de Gruijl JR, De Zeeuw CI (2013) Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation. Front Neural Circuits 7:133Google Scholar
  144. Wulff P, Schonewille M, Renzi M, Viltono L, Sassoe-Pognetto M, Badura A, Gao Z, Hoebeek FE, van Dorp S, Wisden W, Farrant M, De Zeeuw CI (2009) Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci 12:1042–1049.2718327PubMedPubMedCentralCrossRefGoogle Scholar
  145. Yang Y, Lisberger SG (2014) Role of plasticity at different sites across the time course of cerebellar motor learning. J Neurosci 34:7077–7090PubMedPubMedCentralCrossRefGoogle Scholar
  146. Zheng N, Raman IM (2009) Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei. J Neurosci 29:9826–9838PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of BiologyEmory UniversityAtlantaUSA

Section editors and affiliations

  • Donna L. Gruol
    • 1
  1. 1.Molecular and Integrative Neuroscience Department (MIND), The Scripps Research InstituteLa JollaUSA

Personalised recommendations