Development of Physiological Activity in the Cerebellum

  • Sriram Jayabal
  • Alanna J. WattEmail author
Living reference work entry

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One remarkable aspect of cerebellar development is that intrinsic physiological activity of several neuronal cell types, including Purkinje cells, can be observed throughout a large portion of the developmental window. Although ion channels primarily drive this intrinsic activity, it can also be influenced by other cellular properties and inputs, including synaptic and neuromodulatory inputs, calcium buffers, and others. Many of the factors that drive or influence intrinsic activity are expressed in a tightly regulated manner during the development of the cerebellum. Here, we review how the ion channels, calcium buffers, synapses, and neuromodulators that are differentially expressed during development give rise to activity patterns with unique regulatory properties, which may serve important roles in sculpting the developing cerebellum. We also review recent lines of evidence that suggest changes in synaptic and intrinsic activity may be common developmental changes contributing to the pathophysiology of not only cerebellar ataxias but also neurodevelopmental diseases such as autism spectrum disorders. Finally, we posit that these findings support a hypothesis for an important role for early physiological activity in the formation of the cerebellum and that alterations in this activity can lead to pathology.


Cerebellum Purkinje cell Ion channels Autism Ataxia Development 


  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(6):e1005578. PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9(5):341–355. PubMedPubMedCentralCrossRefGoogle Scholar
  3. Ackman JB, Burbridge TJ, Crair MC (2012) Retinal waves coordinate patterned activity throughout the developing visual system. Nature 490(7419):219–225. PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ady V, Toscano Marquez B, Nath M, Chang PK, Hui J, Cook AC, Charron F, Lariviere R, Brais B, McKinney RA, Watt AJ (2018) Altered synaptic and intrinsic properties of cerebellar Purkinje cells in a mouse model of ARSACS. J Physiol 596(17):4253–4267. PubMedCrossRefPubMedCentralGoogle Scholar
  5. Airaksinen MS, Eilers J, Garaschuk O, Thoenen H, Konnerth A, Meyer M (1997) Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene. Proc Natl Acad Sci U S A 94(4):1488–1493PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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(4):827–835PubMedCrossRefGoogle Scholar
  7. Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. 3. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J Comp Neurol 136(3):269–293. PubMedCrossRefGoogle Scholar
  8. Altman J (1972) Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and of the molecular layer. J Comp Neurol 145(4):399–463PubMedCrossRefGoogle Scholar
  9. Altman J, Bayer SA (1985) Embryonic development of the rat cerebellum. III. Regional differences in the time of origin, migration, and settling of Purkinje cells. J Comp Neurol 231(1):42–65. PubMedCrossRefGoogle Scholar
  10. Alvina K, Khodakhah K (2008) Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats. J Physiol 586(10):2523–2538. PubMedPubMedCentralCrossRefGoogle Scholar
  11. Alviña K, Khodakhah K (2010a) KCa channels as therapeutic targets in episodic ataxia type-2. J Neurosci 30(21):7249–7257. PubMedPubMedCentralCrossRefGoogle Scholar
  12. Alviña K, Khodakhah K (2010b) The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia. J Neurosci 30(21):7258–7268. PubMedPubMedCentralCrossRefGoogle Scholar
  13. Alvina K, Tara E, Khodakhah K (2016) Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons. Neuroscience 322:171–177. PubMedPubMedCentralCrossRefGoogle Scholar
  14. Anheim M, Tranchant C, Koenig M (2012) The autosomal recessive cerebellar ataxias. N Engl J Med 366(7):636–646. PubMedCrossRefGoogle Scholar
  15. Arancillo M, White JJ, Lin T, Stay TL, Sillitoe RV (2015) In vivo analysis of Purkinje cell firing properties during postnatal mouse development. J Neurophysiol 113(2):578–591. PubMedCrossRefGoogle Scholar
  16. Arnold DB, Heintz N (1997) A calcium responsive element that regulates expression of two calcium binding proteins in Purkinje cells. Proc Natl Acad Sci U S A 94(16):8842–8847PubMedPubMedCentralCrossRefGoogle Scholar
  17. Barbeau A (1976) Friedreich’s ataxia 1976-an overview. Can J Neurol Sci 3(4):389–397PubMedCrossRefGoogle Scholar
  18. Beauchet O, Annweiler C, Callisaya ML, De Cock AM, Helbostad JL, Kressig RW, Srikanth V, Steinmetz JP, Blumen HM, Verghese J, Allali G (2016) Poor gait performance and prediction of dementia: results from a meta-analysis. J Am Med Dir Assoc 17(6):482–490. PubMedPubMedCentralCrossRefGoogle Scholar
  19. Becker EB, Oliver PL, Glitsch MD, Banks GT, Achilli F, Hardy A, Nolan PM, Fisher EM, Davies KE (2009) A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc Natl Acad Sci U S A 106(16):6706–6711. PubMedPubMedCentralCrossRefGoogle Scholar
  20. Belmeguenai A, Hosy E, Bengtsson F, Pedroarena CM, Piochon C, Teuling E, He Q, Ohtsuki G, De Jeu MT, Elgersma Y, De Zeeuw CI, Jorntell H, Hansel C (2010) Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells. J Neurosci 30(41):13630–13643. PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bennett JE, Bair W (2015) Refinement and pattern formation in neural circuits by the interaction of traveling waves with spike-timing dependent plasticity. PLoS Comput Biol 11(8):e1004422. PubMedPubMedCentralCrossRefGoogle Scholar
  22. Black JA, Yokoyama S, Higashida H, Ransom BR, Waxman SG (1994) Sodium channel mRNAs I, II and III in the CNS: cell-specific expression. Brain Res Mol Brain Res 22(1–4):275–289PubMedCrossRefGoogle Scholar
  23. Blankenship AG, Feller MB (2010) Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nat Rev Neurosci 11(1):18–29. PubMedCrossRefGoogle Scholar
  24. Bouchard JP, Barbeau A, Bouchard R, Bouchard RW (1978) Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci 5(1):61–69PubMedCrossRefGoogle Scholar
  25. Brysch W, Creutzfeldt OD, Luno K, Schlingensiepen R, Schlingensiepen KH (1991) Regional and temporal expression of sodium channel messenger RNAs in the rat brain during development. Exp Brain Res 86(3):562–567PubMedCrossRefGoogle Scholar
  26. Burbridge TJ, Xu HP, Ackman JB, Ge X, Zhang Y, Ye MJ, Zhou ZJ, Xu J, Contractor A, Crair MC (2014) Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors. Neuron 84(5):1049–1064. PubMedPubMedCentralCrossRefGoogle Scholar
  27. Butts T, Wilson L, Wingate RJT (2018) Specification of granule cells and Purkinje cells. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  28. Caillard O, Moreno H, Schwaller B, Llano I, Celio MR, Marty A (2000) Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity. Proc Natl Acad Sci U S A 97(24):13372–13377. PubMedPubMedCentralCrossRefGoogle Scholar
  29. Campiglio M, Flucher BE (2015) The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels. J Cell Physiol 230(9):2019–2031. PubMedPubMedCentralCrossRefGoogle Scholar
  30. Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35(2):375–475PubMedCrossRefGoogle Scholar
  31. Cingolani LA, Gymnopoulos M, Boccaccio A, Stocker M, Pedarzani P (2002) Developmental regulation of small-conductance Ca2+-activated K+ channel expression and function in rat Purkinje neurons. J Neurosci 22(11):4456–4467. 20026415PubMedCrossRefPubMedCentralGoogle Scholar
  32. Cupolillo D, Hoxha E, Faralli A, De Luca A, Rossi F, Tempia F, Carulli D (2016) Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice. Neuropsychopharmacol 41(6):1457–1466. CrossRefGoogle Scholar
  33. Davis TH, Chen C, Isom LL (2004) Sodium channel beta1 subunits promote neurite outgrowth in cerebellar granule neurons. J Biol Chem 279(49):51424–51432. PubMedCrossRefGoogle Scholar
  34. Dell’Orco JM, Wasserman AH, Chopra R, Ingram MA, Hu YS, Singh V, Wulff H, Opal P, Orr HT, Shakkottai VG (2015) Neuronal atrophy early in degenerative ataxia is a compensatory mechanism to regulate membrane excitability. J Neurosci 35(32):11292–11307. PubMedPubMedCentralCrossRefGoogle Scholar
  35. Dino MR, Willard FH, Mugnaini E (1999) Distribution of unipolar brush cells and other calretinin immunoreactive components in the mammalian cerebellar cortex. J Neurocytol 28(2):99–123PubMedCrossRefGoogle Scholar
  36. Drewe JA, Verma S, Frech G, Joho RH (1992) Distinct spatial and temporal expression patterns of K+ channel mRNAs from different subfamilies. J Neurosci 12(2):538–548PubMedCrossRefGoogle Scholar
  37. Du X, Wang J, Zhu H, Rinaldo L, Lamar KM, Palmenberg AC, Hansel C, Gomez CM (2013) Second cistron in CACNA1A gene encodes a transcription factor mediating cerebellar development and SCA6. Cell 154(1):118–133. PubMedPubMedCentralCrossRefGoogle Scholar
  38. Dupont JL, Gardette R, Crepel F (1987) Postnatal development of the chemosensitivity of rat cerebellar Purkinje cells to excitatory amino acids. An in vitro study. Brain Res 431(1):59–68PubMedCrossRefGoogle Scholar
  39. Durr A, Stevanin G, Cancel G, Duyckaerts C, Abbas N, Didierjean O, Chneiweiss H, Benomar A, Lyon-Caen O, Julien J, Serdaru M, Penet C, Agid Y, Brice A (1996) Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 39(4):490–499. PubMedCrossRefGoogle Scholar
  40. Eccles JC (1973) The cerebellum as a computer: patterns in space and time. J Physiol 229(1):1–32PubMedPubMedCentralCrossRefGoogle Scholar
  41. Edgerton JR, Reinhart PH (2003) Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J Physiol 548(Pt 1):53–69. PubMedPubMedCentralCrossRefGoogle Scholar
  42. Edgley SA, Lidierth M (1987) The discharges of cerebellar Golgi cells during locomotion in the cat. J Physiol 392:315–332PubMedPubMedCentralCrossRefGoogle Scholar
  43. Elsen G, Juric-Sekhar G, Daza R, Hevner R (2018) Development of cerebellar nuclei. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  44. Engert JC, Berube P, Mercier J, Dore C, Lepage P, Ge B, Bouchard JP, Mathieu J, Melancon SB, Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A (2000) ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet 24(2):120–125. PubMedCrossRefGoogle Scholar
  45. Farre-Castany MA, Schwaller B, Gregory P, Barski J, Mariethoz C, Eriksson JL, Tetko IV, Wolfer D, Celio MR, Schmutz I, Albrecht U, Villa AE (2007) Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both. Behav Brain Res 178(2):250–261. PubMedCrossRefGoogle Scholar
  46. Felts PA, Yokoyama S, Dib-Hajj S, Black JA, Waxman SG (1997) Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system. Brain Res Mol Brain Res 45(1):71–82PubMedCrossRefGoogle Scholar
  47. Figueroa KP, Coon H, Santos N, Velazquez L, Mederos LA, Pulst SM (2017) Genetic analysis of age at onset variation in spinocerebellar ataxia type 2. Neurol Genet 3(3):e155. PubMedPubMedCentralCrossRefGoogle Scholar
  48. Fletcher CF, Tottene A, Lennon VA, Wilson SM, Dubel SJ, Paylor R, Hosford DA, Tessarollo L, McEnery MW, Pietrobon D, Copeland NG, Jenkins NA (2001) Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J 15(7):1288–1290PubMedCrossRefGoogle Scholar
  49. Fogel BL, Hanson SM, Becker EB (2015) Do mutations in the murine ataxia gene TRPC3 cause cerebellar ataxia in humans? Mov Disord 30(2):284–286. PubMedCrossRefGoogle Scholar
  50. Forero-Vivas ME, Hernandez-Cruz A (2014) Increased firing frequency of spontaneous action potentials in cerebellar Purkinje neurons of db/db mice results from altered auto-rhythmicity and diminished GABAergic tonic inhibition. Gen Physiol Biophys 33(1):29–41. PubMedCrossRefGoogle Scholar
  51. Forrest MD, Wall MJ, Press DA, Feng J (2012) The sodium-potassium pump controls the intrinsic firing of the cerebellar Purkinje neuron. PLoS One 7(12):e51169. PubMedPubMedCentralCrossRefGoogle Scholar
  52. Forti L, Cesana E, Mapelli J, D’Angelo E (2006) Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells. J Physiol 574(Pt 3):711–729. PubMedCrossRefGoogle Scholar
  53. Fremont R, Calderon DP, Maleki S, Khodakhah K (2014) Abnormal high-frequency burst firing of cerebellar neurons in rapid-onset dystonia-parkinsonism. J Neurosci 34(35):11723–11732. PubMedPubMedCentralCrossRefGoogle Scholar
  54. Fremont R, Tewari A, Khodakhah K (2015) Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism. Neurobiol Dis 82:200–212. PubMedPubMedCentralCrossRefGoogle Scholar
  55. Fry M (2006) Developmental expression of Na+ currents in mouse Purkinje neurons. Eur J Neurosci 24(9):2557–2566. PubMedCrossRefGoogle Scholar
  56. Globas C, du Montcel ST, Baliko L, Boesch S, Depondt C, DiDonato S, Durr A, Filla A, Klockgether T, Mariotti C, Melegh B, Rakowicz M, Ribai P, Rola R, Schmitz-Hubsch T, Szymanski S, Timmann D, Van de Warrenburg BP, Bauer P, Schols L (2008) Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov Disord 23(15):2232–2238. PubMedCrossRefGoogle Scholar
  57. Goldman-Wohl DS, Chan E, Baird D, Heintz N (1994) Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei. J Neurosci 14(2):511–522PubMedCrossRefGoogle Scholar
  58. Gong B, Rhodes KJ, Bekele-Arcuri Z, Trimmer JS (1999) Type I and type II Na(+) channel alpha-subunit polypeptides exhibit distinct spatial and temporal patterning, and association with auxiliary subunits in rat brain. J Comp Neurol 412(2):342–352PubMedCrossRefGoogle Scholar
  59. Gonzalez-Perez V, Xia XM, Lingle CJ (2014) Functional regulation of BK potassium channels by gamma1 auxiliary subunits. Proc Natl Acad Sci U S A 111(13):4868–4873. PubMedPubMedCentralCrossRefGoogle Scholar
  60. Good JM, Mahoney M, Miyazaki T, Tanaka KF, Sakimura K, Watanabe M, Kitamura K, Kano M (2017) Maturation of cerebellar Purkinje cell population activity during postnatal refinement of climbing fiber network. Cell Rep 21(8):2066–2073. PubMedCrossRefGoogle Scholar
  61. Ha S, Lee D, Cho YS, Chung C, Yoo YE, Kim J, Lee J, Kim W, Kim H, Bae YC, Tanaka-Yamamoto K, Kim E (2016) Cerebellar shank2 regulates excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. J Neurosci 36(48): 12129–12143. PubMedCrossRefPubMedCentralGoogle Scholar
  62. Haghdoost-Yazdi H, Janahmadi M, Behzadi G (2008) Iberiotoxin-sensitive large conductance Ca2+ -dependent K+ (BK) channels regulate the spike configuration in the burst firing of cerebellar Purkinje neurons. Brain Res 1212:1–8. PubMedCrossRefGoogle Scholar
  63. Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, Kuroda Y (1995) Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord 25(1):1–18PubMedCrossRefGoogle Scholar
  64. Häusser M, Clark BA (1997) Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19(3):665–678PubMedCrossRefGoogle Scholar
  65. Hong S, Negrello M, Junker M, Smilgin A, Thier P, De Schutter E (2016) Multiplexed coding by cerebellar Purkinje neurons. elife 5:e13810. PubMedPubMedCentralCrossRefGoogle Scholar
  66. Hourez R, Servais L, Orduz D, Gall D, Millard I, de Kerchove d’Exaerde A, Cheron G, Orr HT, Pandolfo M, Schiffmann SN (2011) Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J Neurosci 31(33): 11795–11807. PubMedCrossRefPubMedCentralGoogle Scholar
  67. Hoxha E, Boda E, Montarolo F, Parolisi R, Tempia F (2012) Excitability and synaptic alterations in the cerebellum of APP/PS1 mice. PLoS One 7(4):e34726. PubMedPubMedCentralCrossRefGoogle Scholar
  68. Ibrahim MF, Power EM, Potapov K, Empson RM (2017) Motor and cerebellar architectural abnormalities during the early progression of ataxia in a mouse model of SCA1 and how early prevention leads to a better outcome later in life. Front Cell Neurosci 11:292. PubMedPubMedCentralCrossRefGoogle Scholar
  69. Incecik F, Herguner MO, Mert G, Alabaz D, Altunbasak S (2013) Acute cerebellar ataxia associated with enteric fever in a child: a case report. Turk J Pediatr 55(4):441–442PubMedGoogle Scholar
  70. Inoue T, Lin X, Kohlmeier KA, Orr HT, Zoghbi HY, Ross WN (2001) Calcium dynamics and electrophysiological properties of cerebellar Purkinje cells in SCA1 transgenic mice. J Neurophysiol 85(4):1750–1760PubMedCrossRefGoogle Scholar
  71. Irie T, Matsuzaki Y, Sekino Y, Hirai H (2014) Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells. J Physiol 592(1):229–247. PubMedCrossRefGoogle Scholar
  72. Isaksen TJ, Kros L, Vedovato N, Holm TH, Vitenzon A, Gadsby DC, Khodakhah K, Lykke-Hartmann K (2017) Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump. PLoS Genet 13(5):e1006763. PubMedPubMedCentralCrossRefGoogle Scholar
  73. Jahnsen H (1986) Electrophysiological characteristics of neurones in the guinea-pig deep cerebellar nuclei in vitro. J Physiol 372:129–147PubMedPubMedCentralCrossRefGoogle Scholar
  74. Jayabal S, Ljungberg L, Erwes T, Cormier A, Quilez S, El Jaouhari S, Watt AJ (2015) Rapid onset of motor deficits in a mouse model of spinocerebellar ataxia type 6 precedes late cerebellar degeneration. eNeuro 2(6):1–18CrossRefGoogle Scholar
  75. Jayabal S, Chang HHV, Cullen KE, Watt AJ (2016) 4-Aminopyridine alleviates ataxia and reverses cerebellar output deficiency in a mouse model of spinocerebellar ataxia type 6. Sci Rep 6:29489. PubMedPubMedCentralCrossRefGoogle Scholar
  76. Jayabal S, Ljungberg L, Watt AJ (2017) Transient cerebellar alterations during development prior to obvious motor phenotype in a mouse model of spinocerebellar ataxia type 6. J Physiol 595(3):949–966. PubMedCrossRefGoogle Scholar
  77. Kaneda M, Wakamori M, Ito C, Akaike N (1990) Low-threshold calcium current in isolated Purkinje cell bodies of rat cerebellum. J Neurophysiol 63(5):1046–1051. PubMedCrossRefGoogle Scholar
  78. Kano M, Watanabe M (2018) Synaptogenesis and synapse elimination. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  79. Kasumu AW, Hougaard C, Rode F, Jacobsen TA, Sabatier JM, Eriksen BL, Strobaek D, Liang X, Egorova P, Vorontsova D, Christophersen P, Ronn LC, Bezprozvanny I (2012) Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2. Chem Biol 19(10):1340–1353. PubMedPubMedCentralCrossRefGoogle Scholar
  80. Kawa K (2002) Acute synaptic modulation by nicotinic agonists in developing cerebellar Purkinje cells of the rat. J Physiol 538(Pt 1):87–102PubMedPubMedCentralCrossRefGoogle Scholar
  81. Kemp KC, Cook AJ, Redondo J, Kurian KM, Scolding NJ, Wilkins A (2016) Purkinje cell injury, structural plasticity and fusion in patients with Friedreich’s ataxia. Acta Neuropathol Commun 4(1):53. PubMedPubMedCentralCrossRefGoogle Scholar
  82. Khare S, Nick JA, Zhang Y, Galeano K, Butler B, Khoshbouei H, Rayaprolu S, Hathorn T, Ranum LPW, Smithson L, Golde TE, Paucar M, Morse R, Raff M, Simon J, Nordenskjold M, Wirdefeldt K, Rincon-Limas DE, Lewis J, Kaczmarek LK, Fernandez-Funez P, Nick HS, Waters MF (2017) A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking. PLoS One 12(5):e0173565. PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kim CH, Oh SH, Lee JH, Chang SO, Kim J, Kim SJ (2012) Lobule-specific membrane excitability of cerebellar Purkinje cells. J Physiol 590(2):273–288. PubMedCrossRefGoogle Scholar
  84. Koeppen AH, Davis AN, Morral JA (2011) The cerebellar component of Friedreich’s ataxia. Acta Neuropathol 122(3):323–330. PubMedPubMedCentralCrossRefGoogle Scholar
  85. Koibuchi N, Ikeda Y (2018) Hormones and cerebellar development. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  86. Koziol LF, Budding D, Andreasen N, D’Arrigo S, Bulgheroni S, Imamizu H, Ito M, Manto M, Marvel C, Parker K, Pezzulo G, Ramnani N, Riva D, Schmahmann J, Vandervert L, Yamazaki T (2014) Consensus paper: the cerebellum’s role in movement and cognition. Cerebellum 13(1):151–177. PubMedPubMedCentralCrossRefGoogle Scholar
  87. Kreiner L, Christel CJ, Benveniste M, Schwaller B, Lee A (2010) Compensatory regulation of Cav2.1 Ca2+ channels in cerebellar Purkinje neurons lacking parvalbumin and calbindin D-28k. J Neurophysiol 103(1):371–381. PubMedCrossRefGoogle Scholar
  88. Lariviere R, Gaudet R, Gentil BJ, Girard M, Conte TC, Minotti S, Leclerc-Desaulniers K, Gehring K, McKinney RA, Shoubridge EA, McPherson PS, Durham HD, Brais B (2015) Sacs knockout mice present pathophysiological defects underlying autosomal recessive spastic ataxia of Charlevoix-Saguenay. Hum Mol Genet 24(3):727–739. PubMedCrossRefGoogle Scholar
  89. Leto K, Bartolini A, Yanagawa Y, Obata K, Magrassi L, Schilling K, Rossi F (2009) Laminar fate and phenotype specification of cerebellar GABAergic interneurons. J Neurosci 29(21): 7079–7091. PubMedCrossRefPubMedCentralGoogle Scholar
  90. Levy-Mozziconacci A, Alcaraz G, Giraud P, Boudier JA, Caillol G, Couraud F, Autillo-Touati A (1998) Expression of the mRNA for the beta 2 subunit of the voltage-dependent sodium channel in rat CNS. Eur J Neurosci 10(9):2757–2767PubMedCrossRefGoogle Scholar
  91. Li SJ, Wang Y, Strahlendorf HK, Strahlendorf JC (1993) Serotonin alters an inwardly rectifying current (Ih) in rat cerebellar Purkinje cells under voltage clamp. Brain Res 617(1):87–95PubMedCrossRefGoogle Scholar
  92. Li QH, Nakadate K, Tanaka-Nakadate S, Nakatsuka D, Cui Y, Watanabe Y (2004) Unique expression patterns of 5-HT2A and 5-HT2C receptors in the rat brain during postnatal development: Western blot and immunohistochemical analyses. J Comp Neurol 469(1):128–140. PubMedCrossRefGoogle Scholar
  93. Liljelund P, Netzeband JG, Gruol DL (2000) L-type calcium channels mediate calcium oscillations in early postnatal Purkinje neurons. J Neurosci 20(19):7394–7403PubMedCrossRefPubMedCentralGoogle Scholar
  94. Lim CS, Kim H, Yu NK, Kang SJ, Kim T, Ko HG, Lee J, Yang JE, Ryu HH, Park T, Gim J, Nam HJ, Baek SH, Wegener S, Schmitz D, Boeckers TM, Lee MG, Kim E, Lee JH, Lee YS, Kaang BK (2017) Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice. Neuropharmacology 112(Pt A):104–112. PubMedCrossRefGoogle Scholar
  95. Lin H, Magrane J, Clark EM, Halawani SM, Warren N, Rattelle A, Lynch DR (2017) Early VGLUT1-specific parallel fiber synaptic deficits and dysregulated cerebellar circuit in the KIKO mouse model of Friedreich ataxia. Dis Model Mech 10(12):1529–1538. PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ljungberg L, Lang-Ouellette D, Yang A, Jayabal S, Quilez S, Watt AJ (2016) Transient developmental Purkinje cell axonal torpedoes in healthy and ataxic mouse cerebellum. Front Cell Neurosci 10:248.
  97. 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
  98. Llinas R, Sugimori M (1980) Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol 305:197–213PubMedPubMedCentralCrossRefGoogle Scholar
  99. Mandolesi G, Musella A, Gentile A, Grasselli G, Haji N, Sepman H, Fresegna D, Bullitta S, De Vito F, Musumeci G, Di Sanza C, Strata P, Centonze D (2013) Interleukin-1beta alters glutamate transmission at purkinje cell synapses in a mouse model of multiple sclerosis. J Neurosci 33(29):12105–12121. PubMedCrossRefGoogle Scholar
  100. Mandy W, Lai MC (2016) Annual research review: the role of the environment in the developmental psychopathology of autism spectrum condition. J Child Psychol Psychiatry 57(3):271–292. PubMedCrossRefGoogle Scholar
  101. Manto M (2012) Toxic agents causing cerebellar ataxias. Handb Clin Neurol 103:201–213. PubMedCrossRefGoogle Scholar
  102. Manto M, Marmolino D (2009a) Animal models of human cerebellar ataxias: a cornerstone for the therapies of the twenty-first century. Cerebellum 8(3):137–154. PubMedCrossRefGoogle Scholar
  103. Manto M, Marmolino D (2009b) Cerebellar ataxias. Curr Opin Neurol 22(4):419–429. PubMedCrossRefGoogle Scholar
  104. Mark MD, Krause M, Boele HJ, Kruse W, Pollok S, Kuner T, Dalkara D, Koekkoek S, De Zeeuw CI, Herlitze S (2015) Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity. J Neurosci 35(23):8882–8895. PubMedCrossRefPubMedCentralGoogle Scholar
  105. Martina M, Yao GL, Bean BP (2003) Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. J Neurosci 23(13):5698–5707PubMedCrossRefPubMedCentralGoogle Scholar
  106. Marzban H, Rahimi Balaei M, Hawkes R (2018) Axons from the trigeminal ganglia are the earliest afferent projections to the mouse cerebellum. BioRxiv 212076Google Scholar
  107. McKay BE, Turner RW (2005) Physiological and morphological development of the rat cerebellar Purkinje cell. J Physiol 567(Pt 3):829–850PubMedPubMedCentralCrossRefGoogle Scholar
  108. Meacham CA, White LD, Barone S Jr, Shafer TJ (2003) Ontogeny of voltage-sensitive calcium channel alpha(1A) and alpha(1E) subunit expression and synaptic function in rat central nervous system. Brain Res Dev Brain Res 142(1):47–65PubMedCrossRefGoogle Scholar
  109. Meera P, Pulst SM, Otis TS (2016) Cellular and circuit mechanisms underlying spinocerebellar ataxias. J Physiol. PubMedPubMedCentralCrossRefGoogle Scholar
  110. Meera P, Pulst S, Otis T (2017) A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2. Elife 6:e26377. PubMedPubMedCentralCrossRefGoogle Scholar
  111. Miale IL, Sidman RL (1961) An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp Neurol 4:277–296PubMedCrossRefGoogle Scholar
  112. Milosevic A, Zecevic N (1998) Developmental changes in human cerebellum: expression of intracellular calcium receptors, calcium-binding proteins, and phosphorylated and nonphosphorylated neurofilament protein. J Comp Neurol 396(4):442–460PubMedCrossRefGoogle Scholar
  113. Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME (1992) P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature 355(6363):827–829. PubMedCrossRefGoogle Scholar
  114. Modabbernia A, Velthorst E, Reichenberg A (2017) Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism 8:13. PubMedPubMedCentralCrossRefGoogle Scholar
  115. Moreno H, Rudy B, Llinas R (1997) Beta subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line. Proc Natl Acad Sci U S A 94(25):14042–14047PubMedPubMedCentralCrossRefGoogle Scholar
  116. Muller YL, Yool AJ (1998) Increased calcium-dependent K+ channel activity contributes to the maturation of cellular firing patterns in developing cerebellar Purkinje neurons. Brain Res Dev Brain Res 108(1–2):193–203PubMedCrossRefGoogle Scholar
  117. Mundwiler A, Shakkottai VG (2018) Autosomal-dominant cerebellar ataxias. Handb Clin Neurol 147:173–185. PubMedCrossRefGoogle Scholar
  118. Nam SC, Hockberger PE (1997) Analysis of spontaneous electrical activity in cerebellar Purkinje cells acutely isolated from postnatal rats. J Neurobiol 33(1):18–32PubMedCrossRefGoogle Scholar
  119. Nguyen-Vu TD, Kimpo RR, Rinaldi JM, Kohli A, Zeng H, Deisseroth K, Raymond JL (2013) Cerebellar Purkinje cell activity drives motor learning. Nat Neurosci 16(12):1734–1736. PubMedPubMedCentralCrossRefGoogle Scholar
  120. Oh Y, Sashihara S, Waxman SG (1994) In situ hybridization localization of the Na+ channel beta 1 subunit mRNA in rat CNS neurons. Neurosci Lett 176(1):119–122PubMedCrossRefGoogle Scholar
  121. Oostland M, Sellmeijer J, van Hooft JA (2011) Transient expression of functional serotonin 5-HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum. J Physiol 589(Pt 20):4837–4846. PubMedPubMedCentralCrossRefGoogle Scholar
  122. Oostland M, Buijink MR, van Hooft JA (2013) Serotonergic control of Purkinje cell maturation and climbing fibre elimination by 5-HT3 receptors in the juvenile mouse cerebellum. J Physiol 591(7):1793–1807. PubMedPubMedCentralCrossRefGoogle Scholar
  123. Oostland M, Buijink MR, Teunisse GM, von Oerthel L, Smidt MP, van Hooft JA (2014) Distinct temporal expression of 5-HT(1A) and 5-HT(2A) receptors on cerebellar granule cells in mice. Cerebellum 13(4):491–500. PubMedPubMedCentralCrossRefGoogle Scholar
  124. Paulson HL, Shakkottai VG, Clark HB, Orr HT (2017) Polyglutamine spinocerebellar ataxias – from genes to potential treatments. Nat Rev Neurosci 18(10):613–626. PubMedPubMedCentralCrossRefGoogle Scholar
  125. Perkins EM, Clarkson YL, Sabatier N, Longhurst DM, Millward CP, Jack J, Toraiwa J, Watanabe M, Rothstein JD, Lyndon AR, Wyllie DJ, Dutia MB, Jackson M (2010) Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans. J Neurosci 30(14):4857–4867. PubMedPubMedCentralCrossRefGoogle Scholar
  126. Perkins EM, Suminaite D, Clarkson YL, Lee SK, Lyndon AR, Rothstein JD, Wyllie DJ, Tanaka K, Jackson M (2016) Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of beta-III spectrin and GLAST. Hum Mol Genet 25(20):4448–4461. PubMedPubMedCentralCrossRefGoogle Scholar
  127. Person AL, Raman IM (2012) Synchrony and neural coding in cerebellar circuits. Front Neural Circ 6:97. CrossRefGoogle Scholar
  128. Peter S, Ten Brinke MM, Stedehouder J, Reinelt CM, Wu B, Zhou H, Zhou K, Boele HJ, Kushner SA, Lee MG, Schmeisser MJ, Boeckers TM, Schonewille M, Hoebeek FE, De Zeeuw CI (2016) Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice. Nat Commun 7:12627. PubMedPubMedCentralCrossRefGoogle Scholar
  129. Pibiri V, Gerosa C, Vinci L, Faa G, Ambu R (2017) Immunoreactivity pattern of calretinin in the developing human cerebellar cortex. Acta Histochem 119(3):228–234. PubMedCrossRefGoogle Scholar
  130. Piochon C, Irinopoulou T, Brusciano D, Bailly Y, Mariani J, Levenes C (2007) NMDA receptor contribution to the climbing fiber response in the adult mouse Purkinje cell. J Neurosci 27(40):10797–10809. PubMedCrossRefPubMedCentralGoogle Scholar
  131. Piochon C, Levenes C, Ohtsuki G, Hansel C (2010) Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum. J Neurosci 30(45):15330–15335. PubMedPubMedCentralCrossRefGoogle Scholar
  132. Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, Wan V, Simmons DH, Eissa T, Nakatani J, Cherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang SS, Hansel C (2014) Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun 5:5586. PubMedPubMedCentralCrossRefGoogle Scholar
  133. Power EM, Morales A, Empson RM (2016) Prolonged type 1 metabotropic glutamate receptor dependent synaptic signaling contributes to spino-cerebellar ataxia type 1. J Neurosci 36(18): 4910–4916. PubMedCrossRefPubMedCentralGoogle Scholar
  134. Pratt KG, Hiramoto M, Cline HT (2016) An evolutionarily conserved mechanism for activity-dependent visual circuit development. Front Neural Circ 10:79. CrossRefGoogle Scholar
  135. Raman IM, Bean BP (1997) Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J Neurosci 17(12):4517–4526PubMedCrossRefGoogle Scholar
  136. Raman IM, Bean BP (1999) Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J Neurosci 19(5):1663–1674PubMedCrossRefGoogle Scholar
  137. Ransdell JL, Dranoff E, Lau B, Lo WL, Donermeyer DL, Allen PM, Nerbonne JM (2017) Loss of Navbeta4-mediated regulation of sodium currents in adult Purkinje neurons disrupts firing and impairs motor coordination and balance. Cell Rep 20(6):1502. PubMedCrossRefGoogle Scholar
  138. Renzi M, Farrant M, Cull-Candy SG (2007) Climbing-fibre activation of NMDA receptors in Purkinje cells of adult mice. J Physiol 585(Pt 1):91–101. PubMedPubMedCentralCrossRefGoogle Scholar
  139. Rosenmund C, Legendre P, Westbrook GL (1992) Expression of NMDA channels on cerebellar Purkinje cells acutely dissociated from newborn rats. J Neurophysiol 68(5):1901–1905. PubMedCrossRefGoogle Scholar
  140. Rossi M, Perez-Lloret S, Doldan L, Cerquetti D, Balej J, Millar Vernetti P, Hawkes H, Cammarota A, Merello M (2014) Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur J Neurol 21(4):607–615PubMedCrossRefGoogle Scholar
  141. Saitow F, Nagano M, Suzuki H (2018) Developmental changes in serotonergic modulation of GABAergic synaptic transmission and postsynaptic GABAA receptor composition in the cerebellar nuclei. Cerebellum. PubMedCrossRefGoogle Scholar
  142. Salci Y, Fil A, Keklicek H, Cetin B, Armutlu K, Dolgun A, Tuncer A, Karabudak R (2017) Validity and reliability of the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) in multiple sclerosis patients with ataxia. Mult Scler Relat Disord 18:135–140. PubMedCrossRefGoogle Scholar
  143. Sashihara S, Oh Y, Black JA, Waxman SG (1995) Na+ channel beta 1 subunit mRNA expression in developing rat central nervous system. Brain Res Mol Brain Res 34(2):239–250PubMedCrossRefGoogle Scholar
  144. Schaller KL, Caldwell JH (2000) Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system. J Comp Neurol 420(1):84–97PubMedCrossRefGoogle Scholar
  145. Schaller KL, Krzemien DM, Yarowsky PJ, Krueger BK, Caldwell JH (1995) A novel, abundant sodium channel expressed in neurons and glia. J Neurosci 15(5 Pt 1):3231–3242PubMedCrossRefGoogle Scholar
  146. Schlick B, Flucher BE, Obermair GJ (2010) Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167(3):786–798. PubMedPubMedCentralCrossRefGoogle Scholar
  147. Schmahmann JD (2004) Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 16(3):367–378. PubMedCrossRefGoogle Scholar
  148. Schwaller B, Meyer M, Schiffmann S (2002) ‘New’ functions for ‘old’ proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice. Cerebellum 1(4):241–258. PubMedCrossRefGoogle Scholar
  149. Scoles DR, Meera P, Schneider MD, Paul S, Dansithong W, Figueroa KP, Hung G, Rigo F, Bennett CF, Otis TS, Pulst SM (2017) Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Nature 544(7650):362–366. PubMedPubMedCentralCrossRefGoogle Scholar
  150. Scotti AL, Nitsch C (1992) Differential Ca2+ binding properties in the human cerebellar cortex: distribution of parvalbumin and calbindin D-28k immunoreactivity. Anat Embryol (Berl) 185(2):163–167CrossRefGoogle Scholar
  151. Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT (2006) RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell 127(4):697–708. PubMedCrossRefGoogle Scholar
  152. Shah BS, Stevens EB, Pinnock RD, Dixon AK, Lee K (2001) Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS. J Physiol 534(Pt 3):763–776PubMedPubMedCentralCrossRefGoogle Scholar
  153. Shakkottai VG, Xiao M, Xu L, Wong M, Nerbonne JM, Ornitz DM, Yamada KA (2009) FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol Dis 33(1):81–88. PubMedCrossRefGoogle Scholar
  154. Shakkottai VG, do Carmo Costa M, Dell’Orco JM, Sankaranarayanan A, Wulff H, Paulson HL (2011) Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J Neurosci 31(36):13002–13014. PubMedPubMedCentralCrossRefGoogle Scholar
  155. Shields SD, Cheng X, Gasser A, Saab CY, Tyrrell L, Eastman EM, Iwata M, Zwinger PJ, Black JA, Dib-Hajj SD, Waxman SG (2012) A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis. Ann Neurol 71(2):186–194. PubMedCrossRefGoogle Scholar
  156. Shim HG, Jang SS, Jang DC, Jin Y, Chang W, Park JM, Kim SJ (2016) mGlu1 receptor mediates homeostatic control of intrinsic excitability through Ih in cerebellar Purkinje cells. J Neurophysiol 115(5):2446–2455. PubMedPubMedCentralCrossRefGoogle Scholar
  157. Shim HG, Jang DC, Lee J, Chung G, Lee S, Kim YG, Jeon DE, Kim SJ (2017) Long-term depression of intrinsic excitability accompanied by synaptic depression in cerebellar Purkinje cells. J Neurosci 37(23):5659–5669. PubMedCrossRefPubMedCentralGoogle Scholar
  158. Shuvaev AN, Hosoi N, Sato Y, Yanagihara D, Hirai H (2017) Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice. J Physiol 595(1):141–164. PubMedCrossRefGoogle Scholar
  159. Sillitoe RV, Hawkes R (2018) Zones and stripes: development of cerebellar topography. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  160. Smith SL, Otis TS (2003) Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade. J Neurosci 23(2):367–372PubMedCrossRefPubMedCentralGoogle Scholar
  161. Smith SS, Waterhouse BD, Woodward DJ (1988) Locally applied estrogens potentiate glutamate-evoked excitation of cerebellar Purkinje cells. Brain Res 475(2):272–282PubMedCrossRefGoogle Scholar
  162. Solbach S, Celio MR (1991) Ontogeny of the calcium binding protein parvalbumin in the rat nervous system. Anat Embryol (Berl) 184(2):103–124CrossRefGoogle Scholar
  163. Sotelo C, Rossi F (2018) Purkinje cell migration and differentiation. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F (eds) Handbook of the cerebellum and cerebellar disorders. Springer Science + Business Media, DordrechtGoogle Scholar
  164. Stefanescu MR, Dohnalek M, Maderwald S, Thurling M, Minnerop M, Beck A, Schlamann M, Diedrichsen J, Ladd ME, Timmann D (2015) Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich’s ataxia. Brain 138(Pt 5): 1182–1197. PubMedPubMedCentralCrossRefGoogle Scholar
  165. Stocker M, Pedarzani P (2000) Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol Cell Neurosci 15(5):476–493. PubMedCrossRefGoogle Scholar
  166. Stoodley CJ, Valera EM, Schmahmann JD (2012) Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. NeuroImage 59(2):1560–1570. PubMedCrossRefGoogle Scholar
  167. Stoodley CJ, D’Mello AM, Ellegood J, Jakkamsetti V, Liu P, Nebel MB, Gibson JM, Kelly E, Meng F, Cano CA, Pascual JM, Mostofsky SH, Lerch JP, Tsai PT (2017) Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci 20(12):1744–1751. PubMedPubMedCentralCrossRefGoogle Scholar
  168. Strahlendorf JC, Lee M, Strahlendorf HK (1984) Effects of serotonin on cerebellar Purkinje cells are dependent on the baseline firing rate. Exp Brain Res 56(1):50–58PubMedCrossRefGoogle Scholar
  169. Strahlendorf JC, Strahlendorf HK, Lee M (1986) Enhancement of cerebellar Purkinje cell complex discharge activity by microiontophoretic serotonin. Exp Brain Res 61(3):614–624PubMedCrossRefGoogle Scholar
  170. Sudarov A, Turnbull RK, Kim EJ, Lebel-Potter M, Guillemot F, Joyner AL (2011) Ascl1 genetics reveals insights into cerebellum local circuit assembly. J Neurosci 31(30):11055–11069. PubMedPubMedCentralCrossRefGoogle Scholar
  171. Swensen AM, Bean BP (2003) Ionic mechanisms of burst firing in dissociated Purkinje neurons. J Neurosci 23(29):9650–9663PubMedCrossRefPubMedCentralGoogle Scholar
  172. Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schule R, Haack TB, Schoning M, Biskup S, Rudnik-Schoneborn S, Senderek J, Hoffmann KT, MacLeod P, Schwarz J, Bender B, Kruger S, Kreuz F, Bauer P, Schols L (2013) Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum. Orphanet J Rare Dis 8:41. PubMedPubMedCentralCrossRefGoogle Scholar
  173. Thiffault I, Dicaire MJ, Tetreault M, Huang KN, Demers-Lamarche J, Bernard G, Duquette A, Lariviere R, Gehring K, Montpetit A, McPherson PS, Richter A, Montermini L, Mercier J, Mitchell GA, Dupre N, Prevost C, Bouchard JP, Mathieu J, Brais B (2013) Diversity of ARSACS mutations in French-Canadians. Can J Neurol Sci 40(1):61–66PubMedCrossRefGoogle Scholar
  174. Tian J, Tep C, Benedick A, Saidi N, Ryu JC, Kim ML, Sadasivan S, Oberdick J, Smeyne R, Zhu MX, Yoon SO (2014) p75 regulates Purkinje cell firing by modulating SK channel activity through Rac1. J Biol Chem 289(45):31458–31472. PubMedPubMedCentralCrossRefGoogle Scholar
  175. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, Steinberg J, Crawley JN, Regehr WG, Sahin M (2012) Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488(7413):647–651. PubMedPubMedCentralCrossRefGoogle Scholar
  176. Turrigiano GG (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci 22(5):221–227PubMedCrossRefGoogle Scholar
  177. Vega-Saenz de Miera EC, Rudy B, Sugimori M, Llinas R (1997) Molecular characterization of the sodium channel subunits expressed in mammalian cerebellar Purkinje cells. Proc Natl Acad Sci U S A 94(13):7059–7064PubMedCrossRefGoogle Scholar
  178. Vyklicky V, Korinek M, Smejkalova T, Balik A, Krausova B, Kaniakova M, Lichnerova K, Cerny J, Krusek J, Dittert I, Horak M, Vyklicky L (2014) Structure, function, and pharmacology of NMDA receptor channels. Physiol Res 63(Suppl 1):S191–S203PubMedGoogle Scholar
  179. Walter JT, Alvina K, Womack MD, Chevez C, Khodakhah K (2006) Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci 9(3):389–397. PubMedCrossRefGoogle Scholar
  180. Wang Y, Strahlendorf JC, Strahlendorf HK (1992) Serotonin reduces a voltage-dependent transient outward potassium current and enhances excitability of cerebellar Purkinje cells. Brain Res 571(2):345–349PubMedCrossRefGoogle Scholar
  181. Wang X, Wang H, Xia Y, Jiang H, Shen L, Wang S, Shen R, Huang L, Wang J, Xu Q, Li X, Luo X, Tang B (2010) A neuropathological study at autopsy of early onset spinocerebellar ataxia 6. J Clin Neurosci 17(6):751–755. PubMedCrossRefGoogle Scholar
  182. Wang SS, Kloth AD, Badura A (2014) The cerebellum, sensitive periods, and autism. Neuron 83(3):518–532. PubMedPubMedCentralCrossRefGoogle Scholar
  183. Watanabe S, Takagi H, Miyasho T, Inoue M, Kirino Y, Kudo Y, Miyakawa H (1998) Differential roles of two types of voltage-gated Ca2+ channels in the dendrites of rat cerebellar Purkinje neurons. Brain Res 791(1–2):43–55PubMedCrossRefGoogle Scholar
  184. Watase K, Barrett CF, Miyazaki T, Ishiguro T, Ishikawa K, Hu Y, Unno T, Sun Y, Kasai S, Watanabe M, Gomez CM, Mizusawa H, Tsien RW, Zoghbi HY (2008) Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels. Proc Natl Acad Sci U S A 105(33):11987–11992. PubMedPubMedCentralCrossRefGoogle Scholar
  185. Waters MF, Fee D, Figueroa KP, Nolte D, Muller U, Advincula J, Coon H, Evidente VG, Pulst SM (2005) An autosomal dominant ataxia maps to 19q13: allelic heterogeneity of SCA13 or novel locus? Neurology 65(7):1111–1113. PubMedCrossRefGoogle Scholar
  186. Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JP, Nolte D, Mock AF, Evidente VG, Fee DB, Muller U, Durr A, Brice A, Papazian DM, Pulst SM (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 38(4):447–451. PubMedCrossRefGoogle Scholar
  187. Watt AJ, Cuntz H, Mori M, Nusser Z, Sjöström PJ, Häusser M (2009) Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity. Nat Neurosci 12(4):463–473. PubMedPubMedCentralCrossRefGoogle Scholar
  188. Wefers AK, Haberlandt C, Tekin NB, Fedorov DA, Timmermann A, van der Want JJL, Chaudhry FA, Steinhauser C, Schilling K, Jabs R (2017) Synaptic input as a directional cue for migrating interneuron precursors. Development 144(22):4125–4136. PubMedCrossRefGoogle Scholar
  189. Weiser M, Vega-Saenz de Miera E, Kentros C, Moreno H, Franzen L, Hillman D, Baker H, Rudy B (1994) Differential expression of Shaw-related K+ channels in the rat central nervous system. J Neurosci 14(3 Pt 1):949–972PubMedCrossRefGoogle Scholar
  190. Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TV, Snutch TP, Catterall WA (1995) Immunochemical identification and subcellular distribution of the alpha 1A subunits of brain calcium channels. J Neurosci 15(10):6403–6418PubMedCrossRefGoogle Scholar
  191. Wilkins A (2017) Cerebellar dysfunction in multiple sclerosis. Front Neurol 8:312. PubMedPubMedCentralCrossRefGoogle Scholar
  192. Womack M, Khodakhah K (2002) Active contribution of dendrites to the tonic and trimodal patterns of activity in cerebellar Purkinje neurons. J Neurosci 22(24):10603–10612PubMedCrossRefPubMedCentralGoogle Scholar
  193. Womack MD, Khodakhah K (2003) Somatic and dendritic small-conductance calcium-activated potassium channels regulate the output of cerebellar Purkinje neurons. J Neurosci 23(7): 2600–2607PubMedCrossRefPubMedCentralGoogle Scholar
  194. Womack MD, Chevez C, Khodakhah K (2004) Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J Neurosci 24(40): 8818–8822. PubMedCrossRefPubMedCentralGoogle Scholar
  195. Womack MD, Hoang C, Khodakhah K (2009) Large conductance calcium-activated potassium channels affect both spontaneous firing and intracellular calcium concentration in cerebellar Purkinje neurons. Neuroscience 162(4):989–1000. PubMedPubMedCentralCrossRefGoogle Scholar
  196. Woodward DJ, Hoffer BJ, Lapham LW (1969) Postnatal development of electrical and enzyme histochemical activity in Purkinje cells. Exp Neurol 23(1):120–139PubMedCrossRefGoogle Scholar
  197. Xiao J, Cerminara NL, Kotsurovskyy Y, Aoki H, Burroughs A, Wise AK, Luo Y, Marshall SP, Sugihara I, Apps R, Lang EJ (2014) Systematic regional variations in Purkinje cell spiking patterns. PLoS One 9(8):e105633. PubMedPubMedCentralCrossRefGoogle Scholar
  198. Yashiro K, Philpot BD (2008) Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology 55(7):1081–1094. PubMedPubMedCentralCrossRefGoogle Scholar
  199. Zhou H, Lin Z, Voges K, Ju C, Gao Z, Bosman LW, Ruigrok TJ, Hoebeek FE, De Zeeuw CI, Schonewille M (2014) Cerebellar modules operate at different frequencies. elife 3:e02536. PubMedPubMedCentralCrossRefGoogle Scholar
  200. Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 15(1):62–69. PubMedPubMedCentralCrossRefGoogle Scholar
  201. Zu T, Duvick LA, Kaytor MD, Berlinger MS, Zoghbi HY, Clark HB, Orr HT (2004) Recovery from polyglutamine-induced neurodegeneration in conditional SCA1 transgenic mice. J Neurosci 24(40):8853–8861. PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurobiologyStanford University School of MedicineStanfordUSA
  2. 2.Department of BiologyMcGill UniversityMontrealCanada

Section editors and affiliations

  • Roy V. Sillitoe
    • 1
  1. 1.Department of Pathology and ImmunologyBaylor College of Medicine, Jan and Dan Duncan Neurological Research InstituteHoustonUSA

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