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Bidirectional learning in upbound and downbound microzones of the cerebellum

Abstract

Over the past several decades, theories about cerebellar learning have evolved. A relatively simple view that highlighted the contribution of one major form of heterosynaptic plasticity to cerebellar motor learning has given way to a plethora of perspectives that suggest that many different forms of synaptic and non-synaptic plasticity, acting at various sites, can control multiple types of learning behaviour. However, there still seem to be contradictions between the various hypotheses with regard to the mechanisms underlying cerebellar learning. The challenge is therefore to reconcile these different views and unite them into a single overall concept. Here I review our current understanding of the changes in the activity of cerebellar Purkinje cells in different ‘microzones’ during various forms of learning. I describe an emerging model that indicates that the activity of each microzone is bound to either increase or decrease during the initial stages of learning, depending on the directional and temporal demands of its downstream circuitry and the behaviour involved.

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Fig. 1: Organization of the cerebellar system.
Fig. 2: Upbound and downbound microzone activity.
Fig. 3: Molecular characteristics of microzones.
Fig. 4: Net polarity of downstream circuitry for upbound and downbound microzones.
Fig. 5: Learning behaviour controlled by upbound microzones.
Fig. 6: Learning behaviour controlled by downbound microzones.
Fig. 7: Different microzones can operate in synergy.

References

  1. Popa, L. S. & Ebner, T. J. Cerebellum, predictions and errors. Front. Cell. Neurosci. 12, 524 (2019).

    PubMed  PubMed Central  Google Scholar 

  2. Guo, J. Z. et al. Cortex commands the performance of skilled movement. eLife 4, e10774 (2015).

    PubMed  PubMed Central  Google Scholar 

  3. Sauerbrei, B. A. et al. Cortical pattern generation during dexterous movement is input-driven. Nature 577, 386–391 (2020).

    CAS  PubMed  Google Scholar 

  4. Rodriguez-Molina, V. M., Aertsen, A. & Heck, D. H. Spike timing and reliability in cortical pyramidal neurons: effects of EPSC kinetics, input synchronization and background noise on spike timing. PLoS ONE 2, e319 (2007).

    PubMed  PubMed Central  Google Scholar 

  5. Yeo, C. H., Hardiman, M. J. & Glickstein, M. Classical conditioning of the nictitating membrane response of the rabbit - II. Lesions of the cerebellar cortex. Exp. Brain Res. 60, 99–113 (1985).

    CAS  PubMed  Google Scholar 

  6. Ivry, R. B. & Keele, S. W. Timing functions of the cerebellum. J. Cogn. Neurosci. 1, 136–152 (1989).

    CAS  PubMed  Google Scholar 

  7. Lee, K. H. et al. Circuit mechanisms underlying motor memory formation in the cerebellum. Neuron 86, 529–540 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Gilmer, J. I. & Person, A. L. Morphological constraints on cerebellar granule cell combinatorial diversity. J. Neurosci. 37, 12153–12166 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Narain, D., Remington, E. D., Zeeuw, C. I. D. & Jazayeri, M. A cerebellar mechanism for learning prior distributions of time intervals. Nat. Commun. 9, 469 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. Welsh, J. P., Lang, E. J., Suglhara, I. & Llinás, R. Dynamic organization of motor control within the olivocerebellar system. Nature 374, 450–453 (1995).

    Google Scholar 

  11. Zhou, H. et al. Cerebellar modules operate at different frequencies. eLife 3, e02536 (2014).

    PubMed  PubMed Central  Google Scholar 

  12. Tang, T. et al. Heterogeneity of Purkinje cell simple spike–complex spike interactions: zebrin- and non-zebrin-related variations. J. Physiol. 595, 5341–5357 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. De Zeeuw, C. I. et al. Spatiotemporal firing patterns in the cerebellum. Nat. Rev. Neurosci. 12, 327–344 (2011).

    PubMed  Google Scholar 

  14. Walter, J. T. & Khodakhah, K. The advantages of linear information processing for cerebellar computation. Proc. Natl Acad. Sci. USA 106, 4471–4476 (2009).

    CAS  PubMed  Google Scholar 

  15. Person, A. L. & Raman, I. M. Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei. Nature 481, 502–505 (2012).

    CAS  Google Scholar 

  16. Oscarsson, O. Functional organization of spinocerebellar paths. in Somatosensory System Handbook of Sensory Physiology Vol. 2 (ed. Iggo A.) 339–380 (Springer, 1973).

  17. 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. 32, 565–579 (1978).

    CAS  PubMed  Google Scholar 

  18. Oscarsson, O. Functional units of the cerebellum - sagittal zones and microzones. Trends Neurosci. 2, 143–145 (1979).

    Google Scholar 

  19. Armstrong, D. M. Functional significance of connections of the inferior olive. Physiological Rev. 54, 358–417 (1974).

    CAS  Google Scholar 

  20. Voogd, J. & Glickstein, M. The anatomy of the cerebellum. Trends Neurosci. 21, 370–375 (1998).

    CAS  PubMed  Google Scholar 

  21. Apps, R. & Garwicz, M. Anatomical and physiological foundations of cerebellar information processing. Nat. Rev. Neurosci. 6, 297–311 (2005).

    CAS  PubMed  Google Scholar 

  22. Ito, M. The Cerebellum and Neural Control (Raven Press, 1984).

  23. De Zeeuw, C. I., Wylie, D. R., Digiorgi, P. L. & Simpson, J. I. Projections of individual Purkinje cells of identified zones in the flocculus to the vestibular and cerebellar nuclei in the rabbit. J. Comp. Neurol. 349, 428–447 (1994).

    PubMed  Google Scholar 

  24. Uusisaari, M., Obata, K. & Knöpfel, T. Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei. J. Neurophysiol. 97, 901–911 (2007).

    CAS  PubMed  Google Scholar 

  25. Uusisaari, M. & Knöpfel, T. GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei. Neuroscience 156, 537–549 (2008).

    CAS  PubMed  Google Scholar 

  26. Uusisaari, M. & de Schutter, E. The mysterious microcircuitry of the cerebellar nuclei. J. Physiol. 589, 3441–3457 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fujita, H., Kodama, T. & du Lac, S. Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis. eLife 9, e58613 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chan-Palay, V. Cytology and organization in the nucleus lateralis of the cerebellum: The projections of neurons and their processes into afferent axon bundles. Z. Anat. Entwicklungsgesch. 141, 151–159 (1973).

    CAS  PubMed  Google Scholar 

  29. Gornati, S. V. in Cerebello-Thalamic Connection: A Study of Development, Physiology and Anatomy 55–79 (Erasmus University Rotterdam, 2018).

  30. Lang, E. J. et al. The Roles of the olivocerebellar pathway in motor learning and motor control. a consensus paper. Cerebellum 16, 230–252 (2017).

    PubMed  PubMed Central  Google Scholar 

  31. Apps, R. et al. Cerebellar modules and their role as operational cerebellar processing units. Cerebellum 17, 654–682 (2018).

    PubMed  PubMed Central  Google Scholar 

  32. Voogd, J., Schraa-Tam, C. K. L., Van Der Geest, J. N. & De Zeeuw, C. I. Visuomotor cerebellum in human and nonhuman primates. in Cerebellum 11, 392–410 (2012).

    PubMed  Google Scholar 

  33. Ruigrok, T. J. H. & Voogd, J. Organization of projections from the inferior olive to the cerebellar nuclei in the rat. J. Comp. Neurol. 426, 209–228 (2000).

    CAS  PubMed  Google Scholar 

  34. Sugihara, I. & Shinoda, Y. Molecular, topographic, and functional organization of the cerebellar cortex: a study with combined aldolase C and olivocerebellar labeling. J. Neurosci. 24, 8771–8785 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Person, A. L. & Raman, I. M. Synchrony and neural coding in cerebellar circuits. Front. Neural Circuits 6, 1–32 (2012).

    Google Scholar 

  36. Herzfeld, D. J., Kojima, Y., Soetedjo, R. & Shadmehr, R. Encoding of action by the Purkinje cells of the cerebellum. Nature 526, 439–441 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Herzfeld, D. J., Kojima, Y., Soetedjo, R. & Shadmehr, R. Encoding of error and learning to correct that error by the Purkinje cells of the cerebellum. Nat. Neurosci. 21, 736–743 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Hesslow, G. Correspondence between climbing fibre input and motor output in eyeblink-related areas in cat cerebellar cortex. J. Physiol. 476, 229–244 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hesslow, G. Inhibition of classically conditioned eyeblink responses by stimulation of the cerebellar cortex in the decerebrate cat. J. Physiol. 476, 245–256 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Simpson, J. I., Wylie, D. R. & De Zeeuw, C. I. On climbing fiber signals and their consequence(s). Behav. Brain Sci. 19, 384–398 (1996).

    Google Scholar 

  41. Medina, J. F., Garcia, K. S., Nores, W. L., Taylor, N. M. & Mauk, M. D. Timing mechanisms in the cerebellum: Testing predictions of a large- scale computer simulation. J. Neurosci. 20, 5516–5525 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Yang, Y. & Lisberger, S. G. Purkinje-cell plasticity and cerebellar motor learning are graded by complex-spike duration. Nature 510, 529–532 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Chabrol, F. P., Blot, A. & Mrsic-Flogel, T. D. Cerebellar contribution to preparatory activity in motor neocortex. Neuron 103, 506–519 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Deverett, B., Koay, S. A., Oostland, M. & Wang, S. S. H. Cerebellar involvement in an evidence-accumulation decision-making task. eLife 7, e36781 (2018).

    PubMed  PubMed Central  Google Scholar 

  45. Heffley, W. & Hull, C. Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum. eLife 8, e46764 (2019).

    PubMed  PubMed Central  Google Scholar 

  46. Kostadinov, D., Beau, M., Pozo, M. B. & Häusser, M. Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells. Nat. Neurosci. 22, 950–962 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Larry, N., Yarkoni, M., Lixenberg, A. & Joshua, M. Cerebellar climbing fibers encode expected reward size. eLife 8, e46870 (2019).

    PubMed  PubMed Central  Google Scholar 

  48. Thach, W. T. Somatosensory receptive fields of single units in cat cerebellar cortex. J. Neurophysiol. 30, 675–696 (1967).

    PubMed  Google Scholar 

  49. White, J. J. & Sillitoe, R. V. Genetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice. Nat. Commun. 8, 14912 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Brown, A. M. et al. Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells. Sci. Rep. 9, 1742 (2019).

    PubMed  PubMed Central  Google Scholar 

  51. Marr, D. A theory of cerebellar cortex. J. Physiol. 202, 437–470 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Albus, J. S. A theory of cerebellar function. Math. Biosci. 10, 25–61 (1971).

    Google Scholar 

  53. Gao, Z., Van Beugen, B. J. & De Zeeuw, C. I. Distributed synergistic plasticity and cerebellar learning. Nat. Rev. Neurosci. 13, 619–635 (2012).

    CAS  PubMed  Google Scholar 

  54. Ito, M. Bases and implications of learning in the cerebellum - adaptive control and internal model mechanism. Prog. Brain Res. 148, 95–109 (2005).

    PubMed  Google Scholar 

  55. Wang, S. S. H., Denk, W. & Häusser, M. Coincidence detection in single dendritic spines mediated by calcium release. Nat. Neurosci. 3, 1266–1273 (2000).

    CAS  PubMed  Google Scholar 

  56. Coesmans, M., Weber, J. T., De Zeeuw, C. I. & Hansel, C. Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control. Neuron 44, 691–700 (2004).

    CAS  PubMed  Google Scholar 

  57. Hansel, C. et al. αCaMKII is essential for cerebellar LTD and motor learning. Neuron 51, 835–843 (2006).

    CAS  PubMed  Google Scholar 

  58. Suvrathan, A., Payne, H. L. & Raymond, J. L. Timing rules for synaptic plasticity matched to behavioral function. Neuron 92, 959–967 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Kassardjian, C. D. et al. The site of a motor memory shifts with consolidation. J. Neurosci. 25, 7979–7985 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Carulli, D. et al. Cerebellar plasticity and associative memories are controlled by perineuronal nets. Proc. Natl Acad. Sci. USA 117, 6855–6865 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Gittis, A. H. & du Lac, S. Intrinsic and synaptic plasticity in the vestibular system. Curr. Opin. Neurobiol. 16, 385–390 (2006).

    CAS  PubMed  Google Scholar 

  62. Kim, S. J. & Linden, D. J. Ubiquitous plasticity and memory storage. Neuron 56, 582–592 (2007).

    CAS  PubMed  Google Scholar 

  63. Medina, J. F. & Lisberger, S. G. Encoding and decoding of learned smooth-pursuit eye movements in the floccular complex of the monkey cerebellum. J. Neurophysiol. 102, 2039–2054 (2009).

    PubMed  PubMed Central  Google Scholar 

  64. Schonewille, M. et al. Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning. Neuron 67, 618–628 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Schonewille, M. et al. Reevaluating the role of LTD in cerebellar motor learning. Neuron 70, 43–50 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Boele, H. J., Koekkoek, S. K. E., De Zeeuw, C. I. & Ruigrok, T. J. H. Axonal sprouting and formation of terminals in the adult cerebellum during associative motor learning. J. Neurosci. 33, 17897–17907 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Gao, Z. et al. Excitatory cerebellar nucleocortical circuit provides internal amplification during associative conditioning. Neuron 89, 645–657 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Gutierrez-Castellanos, N. et al. Motor learning requires Purkinje cell synaptic potentiation through activation of AMPA-receptor subunit GluA3. Neuron 93, 409–424 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. De Zeeuw, C. I. & Ten Brinke, M. M. Motor learning and the cerebellum. Cold Spring Harb. Perspect. Biol. 7, a021683 (2015).

    PubMed  PubMed Central  Google Scholar 

  70. Medina, J. F., Nores, W. L. & Mauk, M. D. Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature 416, 330–333 (2002).

    CAS  PubMed  Google Scholar 

  71. Ohmae, S. & Medina, J. F. Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice. Nat. Neurosci. 18, 1798–1803 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. ten Brinke, M. M. et al. Evolving models of Pavlovian conditioning: cerebellar cortical dynamics in awake behaving mice. Cell Rep. 13, 1977–1988 (2015).

    PubMed  PubMed Central  Google Scholar 

  73. Voges, K., Wu, B., Post, L., Schonewille, M. & De Zeeuw, C. I. Mechanisms underlying vestibulo-cerebellar motor learning in mice depend on movement direction. J. Physiol. 595, 5301–5326 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Streng, M. L., Popa, L. S. & Ebner, T. J. Modulation of sensory prediction error in Purkinje cells during visual feedback manipulations. Nat. Commun. 9, 1099 (2018).

    PubMed  PubMed Central  Google Scholar 

  75. Gaffield, M. A., Bonnan, A. & Christie, J. M. Conversion of graded presynaptic climbing fiber activity into graded postsynaptic Ca2+ signals by Purkinje cell dendrites. Neuron 102, 762–769 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Ju, C. et al. Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control. J. Physiol. 597, 2483–2514 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Carta, I., Chen, C. H., Schott, A. L., Dorizan, S. & Khodakhah, K. Cerebellar modulation of the reward circuitry and social behavior. Science 363, 248–258 (2019).

    Google Scholar 

  78. Gao, Z. et al. A cortico-cerebellar loop for motor planning. Nature 563, 113–116 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Sendhilnathan, N., Ipata, A. E. & Goldberg, M. E. Neural Correlates of Reinforcement Learning in Mid-lateral Cerebellum. Neuron 106, 188–198 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Ramon y Cajal, S. R. Textura del Sistema Nervioso del Hombre y de los Vertebrados (Moya, 1904).

  81. Voogd, J. The Cerebellum of the Cat. (Van Gorcum, Assen, 1964).

  82. Graham, D. J. & Wylie, D. R. Zebrin-immunopositive and -immunonegative stripe pairs represent functional units in the pigeon vestibulocerebellum. J. Neurosci. 32, 12769–12779 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Pakan, J. M. P., Graham, D. J., Gutiérrez-Ibánez, C. & Wylie, D. R. Organization of the cerebellum: Correlating zebrin immunochemistry with optic flow zones in the pigeon flocculus. Vis. Neurosci. 28, 163–174 (2011).

    PubMed  Google Scholar 

  84. Bengtsson, F. & Hesslow, G. Cerebellar control of the inferior olive. Cerebellum 5, 7–14 (2006).

    CAS  PubMed  Google Scholar 

  85. Mostofi, A., Holtzman, T., Grout, A. S., Yeo, C. H. & Edgley, S. A. Electrophysiological localization of eyeblink-related microzones in rabbit cerebellar cortex. J. Neurosci. 30, 8920–8934 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Sánchez-Campusano, R., Gruart, A., Fernández-Mas, R. & Delgado-García, J. M. An agonist-antagonist cerebellar nuclear system controlling eyelid kinematics during motor learning. Front. Neuroanat. https://doi.org/10.3389/fnana.2012.00008 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ohmae, S. et al. Firing rate modulation of two antagonistic Purkinje cell populations during motor timing in mice. Soc. Neurosci. Abstr. (2014).

  88. ten Brinke, M. M. et al. Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice. eLife 6, e28132 (2017).

    PubMed  PubMed Central  Google Scholar 

  89. Tsutsumi, S. et al. Modular organization of cerebellar climbing fiber inputs during goal-directed behavior. eLife 8, e47021 (2019).

    PubMed  PubMed Central  Google Scholar 

  90. Ito, M., Yoshida, M., Obata, K., Kawai, N. & Udo, M. Inhibitory control of intracerebellar nuclei by the Purkinje cell axons. Exp. Brain Res. 10, 64–80 (1970).

    CAS  PubMed  Google Scholar 

  91. Badura, A. et al. Climbing fiber input shapes reciprocity of Purkinje cell firing. Neuron 78, 700–713 (2013).

    CAS  PubMed  Google Scholar 

  92. Badura, A., Clopath, C., Schonewille, M. & De Zeeuw, C. I. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments. Sci. Rep. 6, 36131 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Xiao, J. et al. Systematic regional variations in Purkinje cell spiking patterns. PLoS ONE 9, e105633 (2014).

    PubMed  PubMed Central  Google Scholar 

  94. Cerminara, N. L., Lang, E. J., Sillitoe, R. V. & Apps, R. Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits. Nat. Rev. Neurosci. 16, 79–93 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. White, J. J. et al. Cerebellar zonal patterning relies on Purkinje cell neurotransmission. J. Neurosci. 34, 8231–8245 (2014).

    PubMed  PubMed Central  Google Scholar 

  96. Perkins, E. M. et al. Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells. Hum. Mol. Genet. 27, 2614–2627 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Rodriques, S. G. et al. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363, 1463–1467 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Wu, B. et al. TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells. eLife 8, e45590 (2019).

    PubMed  PubMed Central  Google Scholar 

  99. Paukert, M., Huang, Y. H., Tanaka, K., Rothstein, J. D. & Bergles, D. E. Zones of enhanced glutamate release from climbing fibers in the mammalian cerebellum. J. Neurosci. 30, 7290–7299 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Gao, W., Chen, G., Reinert, K. C. & Ebner, T. J. Cerebellar cortical molecular layer inhibition is organized in parasagittal zones. J. Neurosci. 26, 8377–8387 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Romano, V. et al. Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity. eLife 7, e38852 (2018).

    PubMed  PubMed Central  Google Scholar 

  102. Hesslow, G. & Ivarsson, M. Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. Neuroreport 5, 649–652 (1994).

    CAS  PubMed  Google Scholar 

  103. Jirenhed, D. A., Bengtsson, F. & Hesslow, G. Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. J. Neurosci. 27, 2493–2502 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Jirenhed, D. A. & Hesslow, G. Time course of classically conditioned Purkinje cell response is determined by initial part of conditioned stimulus. J. Neurosci. 31, 9070–9074 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Wetmore, D. Z. et al. Bidirectional plasticity of Purkinje cells matches temporal features of learning. J. Neurosci. 34, 1731–1737 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Halverson, H. E., Khilkevich, A. & Mauk, M. D. Relating cerebellar Purkinje cell activity to the timing and amplitude of conditioned eyelid responses. J. Neurosci. 35, 7813–7832 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Boele, H. J. et al. Impact of parallel fiber to Purkinje cell long-term depression is unmasked in absence of inhibitory input. Sci. Adv. 4, eaas9426 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. De Zeeuw, C. I. & Yeo, C. H. Time and tide in cerebellar memory formation. Curr. Opin. Neurobiol. 15, 667–674 (2005).

    PubMed  Google Scholar 

  109. Gonzalez-Joekes, J. & Schreurs, B. G. Anatomical characterization of a rabbit cerebellar eyeblink premotor pathway using pseudorabies and Identification of a local modulatory network in anterior interpositus. J. Neurosci. 32, 12472–12487 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Lisberger, S. G., Pavelko, T. A., Bronte-Stewart, H. M. & Stone, L. S. 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, 954–973 (1994).

    CAS  PubMed  Google Scholar 

  111. Blazquez, P. M., Hirata, Y. & Highstein, S. M. The vestibulo-ocular reflex as a model system for motor learning: what is the role of the cerebellum? Cerebellum 3, 188–192 (2004).

    PubMed  Google Scholar 

  112. Schonewille, M. et al. Zonal organization of the mouse flocculus: physiology, input, and output. J. Comp. Neurol. 497, 670–682 (2006).

    PubMed  Google Scholar 

  113. Ito, M. Cerebellar learning in the vestibulo-ocular reflex. Trends Cognit. Sci. 2, 313–321 (1998).

    CAS  Google Scholar 

  114. Lisberger, S. G. & Fuchs, A. F. Role of primate flocculus during rapid behavioral modification of vestibuloocular reflex. I. Purkinje cell activity during visually guided horizontal smooth-pursuit eye movements and passive head rotation. J. Neurophysiol. 41, 733–763 (1978).

    CAS  PubMed  Google Scholar 

  115. De Zeeuw, C. I., Wylie, D. R., Stahl, J. S. & Simpson, J. I. Phase relations of Purkinje cells in the rabbit flocculus during compensatory eye movements. J. Neurophysiol. 74, 2051–2064 (1995).

    PubMed  Google Scholar 

  116. Raymond, J. L. & Lisberger, S. G. Neural learning rules for the vestibulo-ocular reflex. J. Neurosci. 18, 9112–9129 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Blazquez, P. M., Hirata, Y., Heiney, S. A., Green, A. M. & Highstein, S. M. Cerebellar signatures of vestibulo-ocular reflex motor learning. J. Neurosci. 23, 9742–9751 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Payne, H. L. et al. Cerebellar Purkinje cells control eye movements with a rapid rate code that is invariant to spike irregularity. eLife 8, e37102 (2019).

    PubMed  PubMed Central  Google Scholar 

  119. Cullen, K. E. The vestibular system: multimodal integration and encoding of self-motion for motor control. Trends Neurosci. 35, 185–196 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Goldberg, J. M. & Fernandez, C. Physiology of peripheral neurons innervating semicircular canals of the squirrel monkey. I. Resting discharge and response to constant angular accelerations. J. Neurophysiol. 34, 635–660 (1971).

    CAS  PubMed  Google Scholar 

  121. Jaarsma, D. et al. The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending inhibitory input to the floccular granule cell layer. J. Comp. Neurol. 526, 2231–2256 (2018).

    CAS  PubMed  Google Scholar 

  122. Zampini, V. et al. Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit. eLife 5, e15872 (2016).

    PubMed  PubMed Central  Google Scholar 

  123. Proville, R. D. et al. Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements. Nat. Neurosci. 17, 1233–1239 (2014).

    CAS  PubMed  Google Scholar 

  124. Chen, S., Augustine, G. J. & Chadderton, P. The cerebellum linearly encodes whisker position during voluntary movement. eLife 5, e10509 (2016).

    PubMed  PubMed Central  Google Scholar 

  125. Brown, S. T. & Raman, I. M. Sensorimotor integration and amplification of reflexive whisking by well-timed spiking in the cerebellar corticonuclear circuit. Neuron 99, 564–575 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Bellavance, M. A. et al. Parallel inhibitory and excitatory trigemino-facial feedback circuitry for reflexive vibrissa movement. Neuron 95, 673–682 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Teune, T. M., Van Der Burg, J., Van Der Moer, J., Voogd, J. & Ruigrok, T. J. H. Topography of cerebellar nuclear projections to the brain stem in the rat. in Prog. Brain Res. 124, 141–172 (2000).

    CAS  PubMed  Google Scholar 

  128. Zerari-Mailly, F., Pinganaud, G., Dauvergne, C., Buisseret, P. & Buisseret-Delmas, C. Trigemino-reticulo-facial and trigemino-reticulo-hypoglossal pathways in the rat. J. Comp. Neurol. 429, 80–93 (2001).

    CAS  PubMed  Google Scholar 

  129. Herfst, L. J. & Brecht, M. Whisker movements evoked by stimulation of single motor neurons in the facial nucleus of the rat. J. Neurophysiol. 99, 2821–2832 (2008).

    PubMed  Google Scholar 

  130. Deschênes, M. et al. Inhibition, not excitation, drives rhythmic whisking. Neuron 90, 374–387 (2016).

    PubMed  PubMed Central  Google Scholar 

  131. Romano, V. et al. Functional convergence of autonomic and sensorimotor processing in the lateral cerebellum. Cell Rep. 32, 107867 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Furuta, T. et al. Inhibitory gating of vibrissal inputs in the brainstem. J. Neurosci. 28, 1789–1797 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Bosman, L. W. J. et al. Anatomical pathways involved in generating and sensing rhythmic whisker movements. Front. Integr. Neurosci. 5, 53 (2011).

    PubMed  PubMed Central  Google Scholar 

  134. Heiney, S. A., Wohl, M. P., Chettih, S. N., Ruffolo, L. I. & Medina, J. F. Cerebellar-dependent expression of motor learning during eyeblink conditioning in head-fixed mice. J. Neurosci. 34, 14845–14853 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Siegel, J. J., Kalmbach, B., Chitwood, R. A. & Mauk, M. D. Persistent activity in a cortical-to-subcortical circuit: Bridging the temporal gap in trace eyelid conditioning. J. Neurophysiol. 107, 50–64 (2012).

    PubMed  Google Scholar 

  136. Halverson, H. E. & Mauk, M. D. Recordings across sessions is the foundation for using eyelid conditioning as a model system to study aging. Soc. Neurosci. Abstr. 591.19 / H (2017).

  137. Johansson, F., Jirenhed, D. A., Rasmussen, A., Zucca, R. & Hesslow, G. Memory trace and timing mechanism localized to cerebellar Purkinje cells. Proc. Natl Acad. Sci. USA 111, 14930–14934 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Szapiro, G. & Barbour, B. Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover. Nat. Neurosci. 10, 735–742 (2007).

    CAS  PubMed  Google Scholar 

  139. ten Brinke, M. M., Boele, H. J. & De Zeeuw, C. I. Conditioned climbing fiber responses in cerebellar cortex and nuclei. Neurosci. Lett. 688, 26–36 (2019).

    PubMed  Google Scholar 

  140. Johansson, F., Carlsson, H. A. E., Rasmussen, A., Yeo, C. H. & Hesslow, G. Activation of a temporal memory in Purkinje cells by the mGluR7 receptor. Cell Rep. 13, 1741–1746 (2015).

    CAS  PubMed  Google Scholar 

  141. Yeo, C. H. & Hesslow, G. Cerebellum and conditioned reflexes. Trends Cognit. Sci. 2, 322–330 (1998).

    CAS  Google Scholar 

  142. Lin, Q. et al. Cerebellar neurodynamics predict decision timing and outcome on the single-trial level. Cell 180, 536–551.e17 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Gornati, S. V. et al. Differentiating cerebellar impact on thalamic nuclei. Cell Rep. 23, 2690–2704 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Galiana, H. L. & Outerbridge, J. S. A bilateral model for central neural pathways in vestibuloocular reflex. J. Neurophysiol. 51, 210–241 (1984).

    CAS  PubMed  Google Scholar 

  145. Dean, P. Simulated recruitment of medial rectus motoneurons by abducens internuclear neurons: Synaptic specificity vs. intrinsic motoneuron properties. J. Neurophysiol. 78, 1531–1549 (1997).

    CAS  PubMed  Google Scholar 

  146. Galliano, E. et al. Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation. Cell Rep. 3, 1239–1251 (2013).

    CAS  PubMed  Google Scholar 

  147. Carcaud, J. et al. Long-lasting visuo-vestibular mismatch in freely-behaving mice reduces the vestibulo-ocular reflex and leads to neural changes in the direct vestibular pathway. eNeuro https://doi.org/10.1523/ENEURO.0290-16.2017 (2017).

  148. Lisberger, S. G., Pavelko, T. A. & Broussard, D. M. Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons. J. Neurophysiol. 72, 928–953 (1994).

    CAS  PubMed  Google Scholar 

  149. Nelson, A. B., Krispel, C. M., Sekirnjak, C. & Lac, S. D. Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40, 609–620 (2003).

    CAS  PubMed  Google Scholar 

  150. Lepora, N. F., Porrill, J., Yeo, C. H., Evinger, C. & Dean, P. Recruitment in retractor bulbi muscle during eyeblink conditioning: EMG analysis and common-drive model. J. Neurophysiol. 102, 2498–2513 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Caggiano, V. et al. Midbrain circuits that set locomotor speed and gait selection. Nature 553, 455–460 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Sarnaik, R. & Raman, I. M. Control of voluntary and optogenetically perturbed locomotion by spike rate and timing of neurons of the mouse cerebellar nuclei. eLife 7, e29546 (2018).

    PubMed  PubMed Central  Google Scholar 

  153. Wagner, M. J. et al. Shared cortex-cerebellum dynamics in the execution and learning of a motor task. Cell 177, 669–682.e24 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Wadiche, J. I. & Jahr, C. E. Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity. Nat. Neurosci. 8, 1329–1334 (2005).

    CAS  PubMed  Google Scholar 

  155. Na, J., Sugihara, I. & Shinoda, Y. The entire trajectories of single pontocerebellar axons and their lobular and longitudinal terminal distribution patterns in multiple aldolase C-positive compartments of the rat cerebellar cortex. J. Comp. Neurol. 527, 2488–2511 (2019).

    CAS  PubMed  Google Scholar 

  156. Lee, S. K., Sillitoe, R. V., Silva, C., Martina, M. & Sekerkova, G. α-Synuclein expression in the mouse cerebellum is restricted to VGluT1 excitatory terminals and is enriched in unipolar brush cells. Cerebellum 14, 516–527 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Valera, A. M. et al. Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex. eLife 5, e09862 (2016).

    PubMed  PubMed Central  Google Scholar 

  158. Witter, L. & De Zeeuw, C. I. In vivo differences in inputs and spiking between neurons in lobules VI/VII of neocerebellum and lobule X of archaeocerebellum. Cerebellum 14, 506–515 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Witter, L. & De Zeeuw, C. I. Regional functionality of the cerebellum. Curr. Opin. Neurobiol. 33, 150–155 (2015).

    CAS  PubMed  Google Scholar 

  160. Rasmussen, A. Graded error signals in eyeblink conditioning. Neurobiol. Learn. Mem. 170, 107023 (2020).

    PubMed  Google Scholar 

  161. Félix-Oliveira, A., Dias, R. B., Colino-Oliveira, M., Rombo, D. M. & Sebastião, A. M. Homeostatic plasticity induced by brief activity deprivation enhances long-term potentiation in the mature rat hippocampus. J. Neurophysiol. 112, 3012–3022 (2014).

    PubMed  Google Scholar 

  162. Womack, M. D. & Khodakhah, K. Dendritic control of spontaneous bursting in cerebellar Purkinje cells. J. Neurosci. 24, 3511–3521 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Van Woerden, G. M. et al. ΒcaMKII controls the direction of plasticity at parallel fiber-Purkinje cell synapses. Nat. Neurosci. 12, 823–825 (2009).

    PubMed  Google Scholar 

  164. Kim, C. H. et al. Lobule-specific membrane excitability of cerebellar Purkinje cells. J. Physiol. 590, 273–288 (2012).

    CAS  PubMed  Google Scholar 

  165. Linden, D. J. A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis. J. Neurophysiol. 107, 448–454 (2012).

    CAS  PubMed  Google Scholar 

  166. Müller, D. et al. Dlk1 promotes a fast motor neuron biophysical signature required for peak force execution. Science 343, 1264–1266 (2014).

    PubMed  Google Scholar 

  167. Witter, L., Canto, C. B., Hoogland, T. M., de Gruijl, J. R. & De Zeeuw, C. I. Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation. Front. Neural Circuits 7, 133 (2013).

    PubMed  PubMed Central  Google Scholar 

  168. Slemmer, J. E., De Zeeuw, C. I. & Weber, J. T. Don’t get too excited: mechanisms of glutamate-mediated Purkinje cell death. Prog. Brain Res. 148, 367–390 (2005).

    CAS  PubMed  Google Scholar 

  169. Chaumont, J. et al. Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge. Proc. Natl Acad. Sci. USA 110, 16223–16228 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Özcan, O. O. et al. Differential coding strategies in glutamatergic and GABAergic neurons in the medial cerebellar nucleus. J. Neurosci. 40, 159–170 (2020).

    PubMed  PubMed Central  Google Scholar 

  171. Ebner, T. J., Yu Qi, X. & Bloedel, J. R. Increase in Purkinje cell gain associated with naturally activated climbing fiber input. J. Neurophysiol. 50, 205–219 (1983).

    CAS  PubMed  Google Scholar 

  172. Stahl, J. S. & Simpson, J. I. Dynamics of rabbit vestibular nucleus neurons and the influence of the flocculus. J. Neurophysiol. 73, 1396–1413 (1995).

    CAS  PubMed  Google Scholar 

  173. Streng, M. L., Popa, L. S. & Ebner, T. J. Climbing fibers control Purkinje cell representations of behavior. J. Neurosci. 37, 1997–2009 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Streng, M. L., Popa, L. S. & Ebner, T. J. Complex spike wars: a new hope. Cerebellum 17, 735–746 (2018).

    PubMed  PubMed Central  Google Scholar 

  175. Yang, Y. & Lisberger, S. G. Role of plasticity at different sites across the time course of cerebellar motor learning. J. Neurosci. 34, 7077–7090 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Junker, M. et al. Learning from the past: a reverberation of past errors in the cerebellar climbing fiber signal. PLoS Biol. 16, e2004344 (2018).

    PubMed  PubMed Central  Google Scholar 

  177. Popa, L. S., Hewitt, A. L. & Ebner, T. J. Purkinje cell simple spike discharge encodes error signals consistent with a forward internal model. in Cerebellum 12, 331–333 (2013).

    PubMed  PubMed Central  Google Scholar 

  178. Catz, N., Dicke, P. W. & Thier, P. Cerebellar-dependent motor learning is based on pruning a Purkinje cell population response. Proc. Natl Acad. Sci. USA 105, 7309–7314 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Fujita, H., Oh-Nishi, A., Obayashi, S. & Sugihara, I. Organization of the marmoset cerebellum in three-dimensional space: Lobulation, aldolase C compartmentalization and axonal projection. J. Comp. Neurol. 518, 1764–1791 (2010).

    CAS  PubMed  Google Scholar 

  180. Luo, Y. et al. Lobular homology in cerebellar hemispheres of humans, non-human primates and rodents: a structural, axonal tracing and molecular expression analysis. Brain Structure Funct. 222, 2449–2472 (2017).

    CAS  Google Scholar 

  181. Jirenhed, D. A., Rasmussen, A., Johansson, F. & Hesslow, G. Learned response sequences in cerebellar Purkinje cells. Proc. Natl Acad. Sci. USA 114, 6127–6132 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Khilkevich, A., Zambrano, J., Richards, M. M. & Mauk, M. D. Cerebellar implementation of movement sequences through feedback. eLife 7, e37443 (2018).

    PubMed  PubMed Central  Google Scholar 

  183. Graf, W., Gerrits, N., Yatim-Dhiba, N. & Ugolini, G. Mapping the oculomotor system: The power of transneuronal labelling with rabies virus. Eur. J. Neurosci. 15, 1557–1562 (2002).

    PubMed  Google Scholar 

  184. De Zeeuw, C. I. & Koekkoek, S. K. E. Signal processing in the C2 module of the flocculus and its role in head movement control. Prog. Brain Res. 114, 299–320 (1997).

    PubMed  Google Scholar 

  185. Vinueza Veloz, M. F. et al. Cerebellar control of gait and interlimb coordination. Brain Struct. Funct. 220, 3513–3536 (2015).

    PubMed  Google Scholar 

  186. Albergaria, C., Silva, N. T., Pritchett, D. L. & Carey, M. R. Locomotor activity modulates associative learning in mouse cerebellum. Nat. Neurosci. 21, 725–735 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Darmohray, D. M., Jacobs, J. R., Marques, H. G. & Carey, M. R. Spatial and temporal locomotor learning in mouse cerebellum. Neuron 102, 217–231.e4 (2019).

    CAS  PubMed  Google Scholar 

  188. Albergaria, C. & Carey, M. R. All Purkinje cells are not created equal. eLife 3, 1–3 (2014).

    Google Scholar 

  189. Grasselli, G. et al. SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning–specific memory traces. PLoS Biol. 18, e3000596 (2020).

    PubMed  PubMed Central  Google Scholar 

  190. Guo, C. et al. Purkinje cells directly inhibit granule cells in specialized regions of the cerebellar cortex. Neuron 91, 1330–1341 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Witter, L., Rudolph, S., Pressler, R. T., Lahlaf, S. I. & Regehr, W. G. Purkinje cell collaterals enable output signals from the cerebellar cortex to feed back to Purkinje cells and interneurons. Neuron 91, 312–319 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is dedicated to J. I. Simpson, former supervisor of the author. The author is funded by the Dutch Organization for Medical Sciences (ZonMw), Life Sciences (ALW-ENW-Klein), the European Research Council (Advanced and Proof of Concept grants), the EU LISTEN Innovative Training Network programme, the Medical NeuroDelta programme, LSH-NWO (Crossover, INTENSE), Albinism Vriendenfonds NIN, van Raamsdonk fonds, and the Trustfonds of Erasmus University, Rotterdam. He is grateful to J. Kruisbrink and S. Wolff who assisted with the bibliography.

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Nature Reviews Neuroscience thanks R. Apps, who co-reviewed with J. Pickford; T. Ebner, who co-reviewed with M. Streng; and G. Hesslow for their contribution to the peer review of this work.

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Glossary

Control system

A system that regulates the behaviour of an animal using control loops.

Training

The process of instructions, rehearsal and feedback that leads to learning.

Cerebellar learning

The induction of a lasting alteration in cerebellar behavior or the potential thereof.

Microzones

Small, sagittally organized networks of cerebellar Purkinje cells and interneurons dedicated to the control of a specific aspect of autonomic, motor or cognitive function.

Microcomplex

A cerebellar cortical microzone of Purkinje cells and an associated small group of cerebellar nucleus cells that are dedicated to the control of a specific aspect of autonomic, motor or cognitive function.

Micromodules

Microcomplexes of Purkinje cells and cerebellar nucleus cells connected with a small cluster of neurons in the inferior olive that together control a specific aspect of autonomic, motor or cognitive function.

Complex spikes

The low-frequency all-or-none spikes of a Purkinje cell that are evoked by activity in its climbing fibre input.

Simple spikes

The high-frequency spikes of a Purkinje cell that are intrinsically generated or evoked by activity in its parallel fibre input.

Long-term depression

(LTD). A process involving postsynaptic changes that renders the synapse less sensitive to an input.

Long-term potentiation

(LTP). A process involving postsynaptic changes that renders the synapse more sensitive to an input.

Net polarity of neurotransmissions

The ultimate excitatory or inhibitory outcome of a set of synapses that connect different neurons in series.

Excitability

The propensity of a neuron to generate, beyond a certain threshold, an output signal (the action potential) from a given input signal.

Floccular complex

The combination of the flocculus and the paraflocculus.

Vestibulocerebellum

The region of the cerebellum that receives prominent inputs from the vestibular apparatus and controls behaviours that depend on the balance of the body in space.

Unipolar brush cells

A class of glutamatergic interneurons found in the granular layer of the cerebellar cortex.

Magnitude sensitivity

The ratio of the amplitude of spike modulation to the amplitude of modulation of the position of a moving part of the body.

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De Zeeuw, C.I. Bidirectional learning in upbound and downbound microzones of the cerebellum. Nat Rev Neurosci 22, 92–110 (2021). https://doi.org/10.1038/s41583-020-00392-x

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