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The basal ganglia and the cerebellum: nodes in an integrated network

Nature Reviews Neurosciencevolume 19pages338350 (2018) | Download Citation


The basal ganglia and the cerebellum are considered to be distinct subcortical systems that perform unique functional operations. The outputs of the basal ganglia and the cerebellum influence many of the same cortical areas but do so by projecting to distinct thalamic nuclei. As a consequence, the two subcortical systems were thought to be independent and to communicate only at the level of the cerebral cortex. Here, we review recent data showing that the basal ganglia and the cerebellum are interconnected at the subcortical level. The subthalamic nucleus in the basal ganglia is the source of a dense disynaptic projection to the cerebellar cortex. Similarly, the dentate nucleus in the cerebellum is the source of a dense disynaptic projection to the striatum. These observations lead to a new functional perspective that the basal ganglia, the cerebellum and the cerebral cortex form an integrated network. This network is topographically organized so that the motor, cognitive and affective territories of each node in the network are interconnected. This perspective explains how synaptic modifications or abnormal activity at one node can have network-wide effects. A future challenge is to define how the unique learning mechanisms at each network node interact to improve performance.

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  1. 1.

    Kemp, J. M. & Powell, T. P. The connexions of the striatum and globus pallidus: synthesis and speculation. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 262, 441–457 (1971).

  2. 2.

    Glickstein, M., May, J. G. 3rd & Mercier, B. E. Corticopontine projection in the macaque: the distribution of labelled cortical cells after large injections of horseradish peroxidase in the pontine nuclei. J. Comp. Neurol. 235, 343–359 (1985).

  3. 3.

    Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986).

  4. 4.

    Middleton, F. A. & Strick, P. L. Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn. 42, 183–200 (2000).

  5. 5.

    Strick, P. L., Dum, R. P. & Fiez, J. A. Cerebellum and nonmotor function. Annu. Rev. Neurosci. 32, 413–434 (2009).

  6. 6.

    Kelly, R. M. & Strick, P. L. Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits. Prog. Brain Res. 143, 449–459 (2004).

  7. 7.

    Kelly, R. M. & Strick, P. L. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J. Neurosci. 23, 8432–8444 (2003).

  8. 8.

    Percheron, G., Francois, C., Talbi, B., Yelnik, J. & Fenelon, G. The primate motor thalamus. Brain Res. Brain Res. Rev. 22, 93–181 (1996).

  9. 9.

    Doya, K. Complementary roles of basal ganglia and cerebellum in learning and motor control. Curr. Opin. Neurobiol. 10, 732–739 (2000). This opinion paper provides a perspective on the learning-oriented specializations of the basal ganglia and the cerebellum.

  10. 10.

    Bostan, A. C., Dum, R. P. & Strick, P. L. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn. Sci. 17, 241–254 (2013).

  11. 11.

    Hoshi, E., Tremblay, L., Feger, J., Carras, P. L. & Strick, P. L. The cerebellum communicates with the basal ganglia. Nat. Neurosci. 8, 1491–1493 (2005). This study provides evidence for the disynaptic pathway from the cerebellar nuclei to the striatum in non-human primates.

  12. 12.

    Bostan, A. C., Dum, R. P. & Strick, P. L. The basal ganglia communicate with the cerebellum. Proc. Natl Acad. Sci. USA 107, 8452–8456 (2010).

  13. 13.

    DeLong, M. & Wichmann, T. Update on models of basal ganglia function and dysfunction. Parkinsonism Relat. Disord. 15 (Suppl. 3), S237–S240 (2009). This study provides evidence for the disynaptic pathway from the STN to the lateral cerebellar cortex in non-human primates.

  14. 14.

    Ichinohe, N., Mori, F. & Shoumura, K. A di-synaptic projection from the lateral cerebellar nucleus to the laterodorsal part of the striatum via the central lateral nucleus of the thalamus in the rat. Brain Res. 880, 191–197 (2000). This study provides evidence for the disynaptic pathway from the deep cerebellar nuclei to the striatum in rats.

  15. 15.

    Chen, C. H., Fremont, R., Arteaga-Bracho, E. E. & Khodakhah, K. Short latency cerebellar modulation of the basal ganglia. Nat. Neurosci. 17, 1767–1775 (2014). This study provides physiological evidence that the cerebellum modulates the striatum through the disynaptic pathway to the striatum in mice.

  16. 16.

    Zemanick, M. C., Strick, P. L. & Dix, R. D. Direction of transneuronal transport of herpes-simplex virus-1 in the primate motor system is strain-dependent. Proc. Natl Acad. Sci. USA 88, 8048–8051 (1991).

  17. 17.

    Parthasarathy, H. B. & Graybiel, A. M. Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrel monkey. J. Neurosci. 17, 2477–2491 (1997).

  18. 18.

    Smith, Y. & Parent, A. Differential connections of caudate nucleus and putamen in the squirrel monkey (Saimiri sciureus). Neuroscience 18, 347–371 (1986).

  19. 19.

    McFarland, N. R. & Haber, S. N. Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque. J. Comp. Neurol. 429, 321–336 (2001).

  20. 20.

    Smith, Y., Raju, D. V., Pare, J. F. & Sidibe, M. The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci. 27, 520–527 (2004).

  21. 21.

    Chen, C. H., Calderon, D. & Khodakhah, K. in The Basal Ganglia. Innovations in Cognitive Neuroscience (ed. Soghomonian, J. J.) 135–153 (Springer, Cham, Switzerland, 2016).

  22. 22.

    Kitai, S. T. & Kita, H. in The Basal Ganglia II. Advances in Behavioral Biology Vol. 32 (eds Carpenter, M. B. & Jayaraman, A) 357–373 (Springer, Boston, 1987).

  23. 23.

    Carpenter, M. B., Carleton, S. C., Keller, J. T. & Conte, P. Connections of the subthalamic nucleus in the monkey. Brain Res. 224, 1–29 (1981).

  24. 24.

    Giolli, R. A. et al. Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey. Vis. Neurosci. 18, 725–740 (2001).

  25. 25.

    Brodal, P. The pontocerebellar projection in the rhesus monkey: an experimental study with retrograde axonal transport of horseradish peroxidase. Neuroscience 4, 193–208 (1979).

  26. 26.

    Jwair, S., Coulon, P. & Ruigrok, T. J. Disynaptic subthalamic input to the posterior cerebellum in rat. Front. Neuroanat. 11, 13 (2017).

  27. 27.

    Moers-Hornikx, V. M. et al. Cerebellar nuclei are activated by high-frequency stimulation of the subthalamic nucleus. Neurosci. Lett. 496, 111–115 (2011).

  28. 28.

    Sutton, A. C., O’Connor, K. A., Pilitsis, J. G. & Shin, D. S. Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats. Brain Struct. Funct. 220, 3595–3609 (2015).

  29. 29.

    Wichmann, T., Bergman, H. & DeLong, M. R. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research. J. Neural Transm. (Vienna) 125, 419–430 (2017).

  30. 30.

    Wu, T. & Hallett, M. The cerebellum in Parkinson’s disease. Brain 136, 696–709 (2013). This article offers a comprehensive review of the role of the cerebellum in PD.

  31. 31.

    Filip, P., Lungu, O. V. & Bares, M. Dystonia and the cerebellum: a new field of interest in movement disorders? Clin. Neurophysiol. 124, 1269–1276 (2013).

  32. 32.

    Caligiore, D. et al. Parkinson’s disease as a system-level disorder. NPJ Parkinsons Dis. 2, 16025 (2016).

  33. 33.

    Shakkottai, V. G. Physiologic changes associated with cerebellar dystonia. Cerebellum 13, 637–644 (2014).

  34. 34.

    Shakkottai, V. G. et al. Current opinions and areas of consensus on the role of the cerebellum in dystonia. Cerebellum 16, 577–594 (2017).

  35. 35.

    DeLong, M. & Wichmann, T. Changing views of basal ganglia circuits and circuit disorders. Clin. EEG Neurosci. 41, 61–67 (2010).

  36. 36.

    Asanuma, K. et al. The metabolic pathology of dopa-responsive dystonia. Ann. Neurol. 57, 596–600 (2005).

  37. 37.

    Wichmann, T., Bergman, H. & DeLong, M. R. The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. J. Neurophysiol. 72, 521–530 (1994).

  38. 38.

    Schrock, L. E., Ostrem, J. L., Turner, R. S., Shimamoto, S. A. & Starr, P. A. The subthalamic nucleus in primary dystonia: single-unit discharge characteristics. J. Neurophysiol. 102, 3740–3752 (2009).

  39. 39.

    Mentis, M. J. et al. Early stage Parkinson’s disease patients and normal volunteers: comparative mechanisms of sequence learning. Hum. Brain Mapp. 20, 246–258 (2003).

  40. 40.

    Zhang, J. et al. Akinetic-rigid and tremor-dominant Parkinson’s disease patients show different patterns of intrinsic brain activity. Parkinsonism Relat. Disord. 21, 23–30 (2015).

  41. 41.

    Lewis, M. M. et al. Task specific influences of Parkinson’s disease on the striato-thalamo-cortical and cerebello-thalamo-cortical motor circuitries. Neuroscience 147, 224–235 (2007).

  42. 42.

    Ballanger, B., Jahanshahi, M., Broussolle, E. & Thobois, S. PET functional imaging of deep brain stimulation in movement disorders and psychiatry. J. Cereb. Blood Flow Metab. 29, 1743–1754 (2009).

  43. 43.

    Palmer, S. J., Li, J., Wang, Z. J. & McKeown, M. J. Joint amplitude and connectivity compensatory mechanisms in Parkinson’s disease. Neuroscience 166, 1110–1118 (2010).

  44. 44.

    Palmer, S. J., Ng, B., Abugharbieh, R., Eigenraam, L. & McKeown, M. J. Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson’s disease. Eur. J. Neurosci. 29, 2187–2196 (2009).

  45. 45.

    Wu, T. et al. Changes of functional connectivity of the motor network in the resting state in Parkinson’s disease. Neurosci. Lett. 460, 6–10 (2009).

  46. 46.

    Wu, T. et al. Effective connectivity of brain networks during self-initiated movement in Parkinson’s disease. Neuroimage 55, 204–215 (2011).

  47. 47.

    Festini, S. B. et al. Altered cerebellar connectivity in Parkinson’s patients ON and OFF L-DOPA medication. Front. Hum. Neurosci. 9, 214 (2015).

  48. 48.

    Payoux, P. et al. Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease. Arch. Neurol. 61, 1307–1313 (2004).

  49. 49.

    Asanuma, K. et al. Network modulation in the treatment of Parkinson’s disease. Brain 129, 2667–2678 (2006).

  50. 50.

    Geday, J., Ostergaard, K., Johnsen, E. & Gjedde, A. STN-stimulation in Parkinson’s disease restores striatal inhibition of thalamocortical projection. Hum. Brain Mapp. 30, 112–121 (2009).

  51. 51.

    Martinu, K. & Monchi, O. Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson’s disease: pathophysiology or compensation? Behav. Neurosci. 127, 222–236 (2013).

  52. 52.

    Mirdamadi, J. L. Cerebellar role in Parkinson’s disease. J. Neurophysiol. 116, 917–919 (2016).

  53. 53.

    Papavassiliou, E. et al. Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Neurosurgery 54, 1120–1129; discussion 1129–1130 (2004).

  54. 54.

    Narabayashi, H., Maeda, T. & Yokochi, F. Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in Parkinsonism. Stereotact. Funct. Neurosurg. 50, 330–337 (1988).

  55. 55.

    Lenz, F. A. et al. Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain 117, 531–543 (1994).

  56. 56.

    Krack, P., Pollak, P., Limousin, P., Benazzouz, A. & Benabid, A. L. Stimulation of subthalamic nucleus alleviates tremor in Parkinson’s disease. Lancet 350, 1675 (1997).

  57. 57.

    Mure, H. et al. Parkinson’s disease tremor-related metabolic network: characterization, progression, and treatment effects. Neuroimage 54, 1244–1253 (2011).

  58. 58.

    Jackson, G. M., Draper, A., Dyke, K., Pepes, S. E. & Jackson, S. R. Inhibition, disinhibition, and the control of action in Tourette syndrome. Trends Cogn. Sci. 19, 655–665 (2015).

  59. 59.

    Worbe, Y., Lehericy, S. & Hartmann, A. Neuroimaging of tic genesis: Present status and future perspectives. Mov. Disord. 30, 1179–1183 (2015).

  60. 60.

    Worbe, Y. et al. Towards a primate model of Gilles de la Tourette syndrome: anatomo-behavioural correlation of disorders induced by striatal dysfunction. Cortex 49, 1126–1140 (2013).

  61. 61.

    McCairn, K. W., Bronfeld, M., Belelovsky, K. & Bar-Gad, I. The neurophysiological correlates of motor tics following focal striatal disinhibition. Brain 132, 2125–2138 (2009).

  62. 62.

    Grabli, D. et al. Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study. Brain 127, 2039–2054 (2004).

  63. 63.

    McCairn, K. W., Iriki, A. & Isoda, M. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition. J. Neurosci. 33, 697–708 (2013).

  64. 64.

    Lerner, A. et al. Widespread abnormality of the gamma-aminobutyric acid-ergic system in Tourette syndrome. Brain 135, 1926–1936 (2012).

  65. 65.

    Neuner, I. et al. Imaging the where and when of tic generation and resting state networks in adult Tourette patients. Front. Hum. Neurosci. 8, 362 (2014).

  66. 66.

    Wang, Z. et al. The neural circuits that generate tics in Tourette’s syndrome. Am. J. Psychiatry 168, 1326–1337 (2011).

  67. 67.

    Menzies, L. et al. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci. Biobehav Rev. 32, 525–549 (2008).

  68. 68.

    Pedroarena-Leal, N. & Ruge, D. Cerebellar neurophysiology in Gilles de la Tourette syndrome and its role as a target for therapeutic intervention. J. Neuropsychol 11, 327–346 (2017).

  69. 69.

    Anticevic, A. et al. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol. Psychiatry 75, 595–605 (2014).

  70. 70.

    Pourfar, M. et al. Abnormal metabolic brain networks in Tourette syndrome. Neurology 76, 944–952 (2011).

  71. 71.

    Feigin, A. et al. Thalamic metabolism and symptom onset in preclinical Huntington’s disease. Brain 130, 2858–2867 (2007).

  72. 72.

    Rub, U. et al. Degeneration of the cerebellum in Huntington’s disease (HD): possible relevance for the clinical picture and potential gateway to pathological mechanisms of the disease process. Brain Pathol. 23, 165–177 (2013).

  73. 73.

    Samson, M. & Claassen, D. O. Neurodegeneration and the cerebellum. Neurodegener Dis. 17, 155–165 (2017).

  74. 74.

    Caligiore, D., Mannella, F., Arbib, M. A. & Baldassarre, G. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome. PLOS Comput. Biol. 13, e1005395 (2017). This article proposes a computational model of how activity in the basal ganglia–cerebellum–cortical network contributes to the generation of motor tics.

  75. 75.

    Mallet, L. et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N. Engl. J. Med. 359, 2121–2134 (2008).

  76. 76.

    Martinez-Torres, I., Hariz, M. I., Zrinzo, L., Foltynie, T. & Limousin, P. Improvement of tics after subthalamic nucleus deep brain stimulation. Neurology 72, 1787–1789 (2009).

  77. 77.

    Breakefield, X. O. et al. The pathophysiological basis of dystonias. Nat. Rev. Neurosci. 9, 222–234 (2008).

  78. 78.

    Argyelan, M. et al. Cerebellothalamocortical connectivity regulates penetrance in dystonia. J. Neurosci. 29, 9740–9747 (2009).

  79. 79.

    Vo, A. et al. Thalamocortical connectivity correlates with phenotypic variability in dystonia. Cereb. Cortex 25, 3086–3094 (2015).

  80. 80.

    Trost, M. et al. Primary dystonia: is abnormal functional brain architecture linked to genotype? Ann. Neurol. 52, 853–856 (2002).

  81. 81.

    Ulug, A. M. et al. Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice. Proc. Natl Acad. Sci. USA 108, 6638–6643 (2011).

  82. 82.

    DeSimone, J. C. et al. In vivo imaging reveals impaired connectivity across cortical and subcortical networks in a mouse model of DYT1 dystonia. Neurobiol. Dis. 95, 35–45 (2016).

  83. 83.

    Calderon, D. P., Fremont, R., Kraenzlin, F. & Khodakhah, K. The neural substrates of rapid-onset Dystonia-Parkinsonism. Nat. Neurosci. 14, 357–365 (2011).

  84. 84.

    Fremont, R., Tewari, A., Angueyra, C. & Khodakhah, K. A role for cerebellum in the hereditary dystonia DYT1. Elife 6, e22775 (2017).

  85. 85.

    Fremont, R., Calderon, D. P., Maleki, S. & Khodakhah, K. Abnormal high-frequency burst firing of cerebellar neurons in rapid-onset dystonia-parkinsonism. J. Neurosci. 34, 11723–11732 (2014).

  86. 86.

    LeDoux, M. S., Lorden, J. F. & Ervin, J. M. Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat. Exp. Neurol. 120, 302–310 (1993).

  87. 87.

    Neychev, V. K., Fan, X., Mitev, V. I., Hess, E. J. & Jinnah, H. A. The basal ganglia and cerebellum interact in the expression of dystonic movement. Brain 131, 2499–2509 (2008).

  88. 88.

    Slaughter, D. G., Nashold, B. S. Jr & Somjen, G. G. Electrical recording with micro- and macroelectrodes from the cerebellum of man. J. Neurosurg. 33, 524–528 (1970).

  89. 89.

    Koch, G. et al. Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients. Brain Stimul. 7, 564–572 (2014).

  90. 90.

    Teixeira, M. J., Schroeder, H. K. & Lepski, G. Evaluating cerebellar dentatotomy for the treatment of spasticity with or without dystonia. Br. J. Neurosurg. 29, 772–777 (2015).

  91. 91.

    Tewari, A., Fremont, R. & Khodakhah, K. It’s not just the basal ganglia: cerebellum as a target for dystonia therapeutics. Mov. Disord. 32, 1537–1545 (2017).

  92. 92.

    Lee, D., Seo, H. & Jung, M. W. Neural basis of reinforcement learning and decision making. Annu. Rev. Neurosci. 35, 287–308 (2012).

  93. 93.

    Watabe-Uchida, M., Eshel, N. & Uchida, N. Neural circuitry of reward prediction error. Annu. Rev. Neurosci. 40, 373–394 (2017).

  94. 94.

    Wagner, M. J., Kim, T. H., Savall, J., Schnitzer, M. J. & Luo, L. Cerebellar granule cells encode the expectation of reward. Nature 544, 96–100 (2017).

  95. 95.

    Garrison, J., Erdeniz, B. & Done, J. Prediction error in reinforcement learning: a meta-analysis of neuroimaging studies. Neurosci. Biobehav Rev. 37, 1297–1310 (2013).

  96. 96.

    Ploghaus, A. et al. Learning about pain: the neural substrate of the prediction error for aversive events. Proc. Natl Acad. Sci. USA 97, 9281–9286 (2000).

  97. 97.

    O’Doherty, J. P., Dayan, P., Friston, K., Critchley, H. & Dolan, R. J. Temporal difference models and reward-related learning in the human brain. Neuron 38, 329–337 (2003).

  98. 98.

    Seymour, B. et al. Temporal difference models describe higher-order learning in humans. Nature 429, 664–667 (2004).

  99. 99.

    Ramnani, N., Elliott, R., Athwal, B. S. & Passingham, R. E. Prediction error for free monetary reward in the human prefrontal cortex. Neuroimage 23, 777–786 (2004).

  100. 100.

    Rodriguez, P. F., Aron, A. R. & Poldrack, R. A. Ventral-striatal/nucleus-accumbens sensitivity to prediction errors during classification learning. Hum. Brain Mapp. 27, 306–313 (2006).

  101. 101.

    Tobler, P. N., O’Doherty, J. P., Dolan, R. J. & Schultz, W. Human neural learning depends on reward prediction errors in the blocking paradigm. J. Neurophysiol. 95, 301–310 (2006).

  102. 102.

    Thoma, P., Bellebaum, C., Koch, B., Schwarz, M. & Daum, I. The cerebellum is involved in reward-based reversal learning. Cerebellum 7, 433–443 (2008).

  103. 103.

    Turner, R. S. & Desmurget, M. Basal ganglia contributions to motor control: a vigorous tutor. Curr. Opin. Neurobiol. 20, 704–716 (2010).

  104. 104.

    Dudman, J. T. & Krakauer, J. W. The basal ganglia: from motor commands to the control of vigor. Curr. Opin. Neurobiol. 37, 158–166 (2016).

  105. 105.

    Turner, R. S., Desmurget, M., Grethe, J., Crutcher, M. D. & Grafton, S. T. Motor subcircuits mediating the control of movement extent and speed. J. Neurophysiol. 90, 3958–3566 (2003).

  106. 106.

    Belkhiria, C. et al. Exploration and identification of cortico-cerebellar-brainstem closed loop during a motivational-motor task: an fMRI study. Cerebellum 16, 326–339 (2017).

  107. 107.

    Wolpert, D. M., Diedrichsen, J. & Flanagan, J. R. Principles of sensorimotor learning. Nat. Rev. Neurosci. 12, 739–751 (2011).

  108. 108.

    Seidler, R. D., Noll, D. C. & Chintalapati, P. Bilateral basal ganglia activation associated with sensorimotor adaptation. Exp. Brain Res. 175, 544–555 (2006).

  109. 109.

    Nikooyan, A. A. & Ahmed, A. A. Reward feedback accelerates motor learning. J. Neurophysiol. 113, 633–646 (2015).

  110. 110.

    Galea, J. M., Mallia, E., Rothwell, J. & Diedrichsen, J. The dissociable effects of punishment and reward on motor learning. Nat. Neurosci. 18, 597–602 (2015).

  111. 111.

    Izawa, J. & Shadmehr, R. Learning from sensory and reward prediction errors during motor adaptation. PLOS Comput. Biol. 7, e1002012 (2011).

  112. 112.

    Hikosaka, O., Nakamura, K., Sakai, K. & Nakahara, H. Central mechanisms of motor skill learning. Curr. Opin. Neurobiol. 12, 217–222 (2002).

  113. 113.

    Doyon, J., Penhune, V. & Ungerleider, L. G. Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia 41, 252–262 (2003).

  114. 114.

    Doyon, J. & Benali, H. Reorganization and plasticity in the adult brain during learning of motor skills. Curr. Opin. Neurobiol. 15, 161–167 (2005).

  115. 115.

    Houk, J. C. Agents of the mind. Biol. Cybern. 92, 427–437 (2005).

  116. 116.

    Taylor, J. A. & Ivry, R. B. Cerebellar and prefrontal cortex contributions to adaptation, strategies, and reinforcement learning. Prog. Brain Res. 210, 217–253 (2014). This article offers a comprehensive review of the contributions of the cerebellum to error-based and reward-based learning.

  117. 117.

    Doyon, J. et al. Contributions of the basal ganglia and functionally related brain structures to motor learning. Behav. Brain Res. 199, 61–75 (2009).

  118. 118.

    Doyon, J. et al. Experience-dependent changes in cerebellar contributions to motor sequence learning. Proc. Natl Acad. Sci. USA 99, 1017–1022 (2002).

  119. 119.

    Lehericy, S. et al. Distinct basal ganglia territories are engaged in early and advanced motor sequence learning. Proc. Natl Acad. Sci. USA 102, 12566–12571 (2005). This fMRI study shows a similar time course of activation in the STN and the lateral cerebellum during sequence learning.

  120. 120.

    Sami, S., Robertson, E. M. & Miall, R. C. The time course of task-specific memory consolidation effects in resting state networks. J. Neurosci. 34, 3982–3992 (2014).

  121. 121.

    Gheysen, F. et al. Taking the brakes off the learning curve. Hum. Brain Mapp. 38, 1676–1691 (2017).

  122. 122.

    Tzvi, E., Stoldt, A., Witt, K. & Kramer, U. M. Striatal-cerebellar networks mediate consolidation in a motor sequence learning task: An fMRI study using dynamic causal modelling. Neuroimage 122, 52–64 (2015).

  123. 123.

    Fermin, A. S. et al. Model-based action planning involves cortico-cerebellar and basal ganglia networks. Sci. Rep. 6, 31378 (2016). This fMRI study provides evidence that different learning strategies recruit distinct basal ganglia–cerebellum–cortical networks.

  124. 124.

    Habas, C. et al. Distinct cerebellar contributions to intrinsic connectivity networks. J. Neurosci. 29, 8586–8594 (2009).

  125. 125.

    Cauda, F. et al. Functional connectivity and coactivation of the nucleus accumbens: a combined functional connectivity and structure-based meta-analysis. J. Cogn. Neurosci 23, 2864–2877 (2011).

  126. 126.

    Li, C. S. et al. Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age. Neuroimage 97, 321–332 (2014).

  127. 127.

    Zheng, W., Liu, X., Song, H., Li, K. & Wang, Z. Altered functional connectivity of cognitive-related cerebellar subregions in Alzheimer’s Disease. Front. Aging Neurosci. 9, 143 (2017).

  128. 128.

    Caulfield, M. D., Zhu, D. C., McAuley, J. D. & Servatius, R. J. Individual differences in resting-state functional connectivity with the executive network: support for a cerebellar role in anxiety vulnerability. Brain Struct. Funct. 221, 3081–3093 (2016).

  129. 129.

    Harding, I. H. et al. Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: The IMAGE-FRDA study. Hum. Brain Mapp. 37, 338–350 (2016).

  130. 130.

    Pereira, L. et al. Resting-state functional connectivity and cognitive dysfunction correlations in spinocerebelellar ataxia type 6 (SCA6). Hum. Brain Mapp. 38, 3001–3010 (2017).

  131. 131.

    Peters, S. K., Dunlop, K. & Downar, J. Cortico-striatal-thalamic loop circuits of the salience network: a central pathway in psychiatric disease and treatment. Front. Syst. Neurosci. 10, 104 (2016).

  132. 132.

    Snider, R. S., Maiti, A. & Snider, S. R. Cerebellar pathways to ventral midbrain and nigra. Exp. Neurol. 53, 714–728 (1976).

  133. 133.

    Watabe-Uchida, M., Zhu, L., Ogawa, S. K., Vamanrao, A. & Uchida, N. Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74, 858–873 (2012).

  134. 134.

    Snider, R. S., Maiti, A. & Snider, S. R. Cerebellar connections to catecholamine systems: anatomical and biochemical studies. Trans. Am. Neurol. Assoc. 101, 295–297 (1976).

  135. 135.

    Nieoullon, A., Cheramy, A. & Glowinski, J. Release of dopamine in both caudate nuclei and both substantia nigrae in response to unilateral stimulation of cerebellar nuclei in the cat. Brain Res. 148, 143–152 (1978).

  136. 136.

    Pelzer, E. A. et al. Cerebellar networks with basal ganglia: feasibility for tracking cerebello-pallidal and subthalamo-cerebellar projections in the human brain. Eur. J. Neurosci. 38, 3106–3114 (2013).

  137. 137.

    Milardi, D. et al. Extensive direct subcortical cerebellum-basal ganglia connections in human brain as revealed by constrained spherical deconvolution tractography. Front. Neuroanat. 10, 29 (2016).

  138. 138.

    Cacciola, A. et al. The known and missing links between the cerebellum, basal ganglia, and cerebral cortex. Cerebellum 16, 753–755 (2017).

  139. 139.

    Cacciola, A. et al. A connectomic analysis of the human basal ganglia network. Front. Neuroanat. 11, 85 (2017).

  140. 140.

    Caligiore, D. et al. Consensus paper: towards a systems-level view of cerebellar function: the interplay between cerebellum, basal ganglia, and cortex. Cerebellum 16, 203–229 (2017).

  141. 141.

    Doya, K. What are the computations of the cerebellum, the basal ganglia and the cerebral cortex? Neural Netw. 12, 961–974 (1999).

  142. 142.

    Sakai, K. et al. Neural representation of a rhythm depends on its interval ratio. J. Neurosci. 19, 10074–10081 (1999).

  143. 143.

    Sakai, K. et al. What and when: parallel and convergent processing in motor control. J. Neurosci. 20, 2691–2700 (2000).

  144. 144.

    Isoda, M. & Hikosaka, O. Switching from automatic to controlled action by monkey medial frontal cortex. Nat. Neurosci. 10, 240–248 (2007).

  145. 145.

    Isoda, M. & Hikosaka, O. Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement. J. Neurosci. 28, 7209–7218 (2008).

  146. 146.

    Hikosaka, O. & Isoda, M. Switching from automatic to controlled behavior: cortico-basal ganglia mechanisms. Trends Cogn. Sci. 14, 154–161 (2010).

  147. 147.

    Pasquereau, B. & Turner, R. S. A selective role for ventromedial subthalamic nucleus in inhibitory control. Elife 6, e31627 (2017).

  148. 148.

    Barton, R. A. & Venditti, C. Rapid evolution of the cerebellum in humans and other great apes. Curr. Biol. 24, 2440–2444 (2014).

  149. 149.

    Stephenson-Jones, M., Ericsson, J., Robertson, B. & Grillner, S. Evolution of the basal ganglia: dual-output pathways conserved throughout vertebrate phylogeny. J. Comp. Neurol. 520, 2957–2973 (2012).

  150. 150.

    Takada, M., Nishihama, M. S., Nishihama, C. C. & Hattori, T. Two separate neuronal populations of the rat subthalamic nucleus project to the basal ganglia and pedunculopontine tegmental region. Brain Res. 442, 72–80 (1988).

  151. 151.

    Woolf, N. J. & Butcher, L. L. Cholinergic systems in the rat brain: IV. Descending projections of the pontomesencephalic tegmentum. Brain Res. Bull. 23, 519–540 (1989).

  152. 152.

    Ruggiero, D. A., Anwar, M., Golanov, E. V. & Reis, D. J. The pedunculopontine tegmental nucleus issues collaterals to the fastigial nucleus and rostral ventrolateral reticular nucleus in the rat. Brain Res. 760, 272–276 (1997).

  153. 153.

    Vitale, F. et al. Cholinergic excitation from the pedunculopontine tegmental nucleus to the dentate nucleus in the rat. Neuroscience 317, 12–22 (2016).

  154. 154.

    Dum, R. P. & Strick, P. L. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J. Neurophysiol. 89, 634–639 (2003).

  155. 155.

    Clower, D. M., Dum, R. P. & Strick, P. L. Basal ganglia and cerebellar inputs to ‘AIP’. Cereb. Cortex 15, 913–920 (2005).

  156. 156.

    Akkal, D., Dum, R. P. & Strick, P. L. Supplementary motor area and presupplementary motor area: targets of basal ganglia and cerebellar output. J. Neurosci. 27, 10659–10673 (2007).

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The preparation of this manuscript was supported in part by US National Institutes of Health grants R01 NS24328, P40 OD010996 and P30 NS076405 (all to P.L.S.).

Reviewer information

Nature Reviews Neuroscience thanks O. Hikosaka, K. Khodakhah and S. Wang for their contribution to the peer review of this work.

Author information


  1. Systems Neuroscience Center and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA

    • Andreea C. Bostan
    •  & Peter L. Strick
  2. University of Pittsburgh Brain Institute and Departments of Neurobiology, Neuroscience and Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    • Peter L. Strick


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Both authors researched data for the article, made a substantial contribution to the discussion of content and contributed to the writing, reviewing and editing of the manuscript before submission.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Andreea C. Bostan or Peter L. Strick.


Rabies virus

An RNA virus that is highly neurotropic and can be used as a retrograde transneuronal tracer. Rabies virus is transported retrogradely to neurons that project to an injection site (that is, first-order neurons). The virus replicates in the first-order neurons and is transmitted transneuronally to neurons that project to the first-order neurons. The virus continues to replicate and move transneuronally through chains of synaptically connected neurons in a time-dependent fashion.

Direct pathway

A monosynaptic pathway that connects one type of MSN in the striatum with neurons in the GPi and the SNpr.

Indirect pathway

A polysynaptic pathway that connects another type of MSN in the striatum to neurons in the GPi and the SNpr.

Reward-based (reinforcement) learning

Learning process (algorithm) that allows reward signals to optimize performance.

Error-based learning

Learning process (algorithm) that allows error signals to improve performance in a gradual manner.

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