Skip to main content
Log in

Cerebellar control of the inferior olive

  • Review Article
  • Scientific Papers
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

A subpopulation of neurones in the cerebellar nuclei projects to the inferior olive, the source of the climbing fibre input to the cerebellum. This nucleo-olivary projection follows the zonal and, probably also, the microzonal arrangement of the cerebellum so that closed loops are formed between the neurones in the olive, the cerebellar cortex and the nuclei. The nucleo-olivary pathway is GABAergic, but several investigators argue that its main effect is to regulate electrotonic coupling between cells in the inferior olive rather than inhibit the olive. However, there is now strong evidence that the nucleo-olivary fibres do inhibit the olive. Three functions have been suggested for this inhibition: (i) feedback control of background activity in Purkinje cells, (ii) feedback control of learning, and (iii) gating of olivary input in general. Evidence is consistent with (i) and (ii). Activity in the nucleo-olivary pathway suppresses both synaptic transmission and background activity in the olive. When learned blink responses develop, the blink related part of the olive is inhibited while blinks are produced. When the nucleo-olivary pathway is interrupted, there is a corresponding increase in complex spike discharge in Purkinje cells followed by a strong suppression of simple spike firing. Stimulation of the pathway has the opposite results. It is concluded that the nucleo-olivary fibres are inhibitory and that they form a number of independent feedback loops, each one specific for a microcomplex, that regulate cerebellar learning as well as spontaneous activity in the olivo-cerebellar circuit.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Graybiel AM, Nauta HJ, Lasek RJ, Nauta WJ. A cerebelloolivary pathway in the cat: An experimental study using autoradiographic tracing technics. Brain Res. 1973;58:205–11.

    Article  PubMed  CAS  Google Scholar 

  2. Legendre A, Courville J. Origin and trajectory of the cerebello-olivary projection: An experimental study with radioactive and fluorescent tracers in the cat. Neuroscience. 1987;21:877–91.

    Article  PubMed  CAS  Google Scholar 

  3. Martin GF, Henkel CK, King JS. Cerebello-olivary fibers: Their origin, course and distribution in the North American opossum. Exp Brain Res. 1976;24:219–36.

    Article  PubMed  CAS  Google Scholar 

  4. Dietrichs E, Walberg F. Direct bidirectional connections between the inferior olive and the cerebellar nuclei. In: Strata P, editor. The olivocerbellar system in motor control. Berlin: Springer-Verlag; 1989. pp 61–81.

    Google Scholar 

  5. Ban M, Ohno T. Projection of cerebellar nuclear neurones to the inferior olive by descending collaterals of ascending fibres. Brain Res. 1977;133:156–61.

    Article  PubMed  CAS  Google Scholar 

  6. Ito M. The cerebellum and neuronal control. New York: Raven Press; 1984.

    Google Scholar 

  7. Tsukahara N, Bando T, Murakami F, Oda Y. Properties of cerebello-precerebellar reverberating circuits. Brain Res. 1983;274:249–59.

    Article  PubMed  CAS  Google Scholar 

  8. Hesslow G. Inhibition of inferior olivary transmission by mesencephalic stimulation in the cat. Neurosci Lett. 1986;63:76–80.

    Article  PubMed  CAS  Google Scholar 

  9. Nelson B, Mugnaini E. Origins of GABA-ergic inputs to the inferior olive. In: Strata P, editor. The olivocerebellar system in motor control. Berlin, Heidelberg, New York, London, Paris, Tokyo: Springer-Verlag; 1989. pp 86–107.

    Google Scholar 

  10. Andersson G, Garwicz M, Hesslow G. Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat. Exp Brain Res. 1988;72:450–6.

    Article  PubMed  CAS  Google Scholar 

  11. Tolbert DL, Massopust LC, Murphy MG, Young PA. The anatomical organization of the cerebello-olivary projection in the cat. J Comp Neurol. 1976;170:525–44.

    Article  PubMed  CAS  Google Scholar 

  12. Dietrichs E, Walberg F. The cerebellar nucleo-olivary projection in the cat. Anat Embryol (Berl) 1981;162:51–67.

    Article  CAS  Google Scholar 

  13. Ruigrok TJ, Voogd J. Cerebellar nucleo-olivary projections in the rat: An anterograde tracing study with Phaseolus vulgarisleucoagglutinin (PHA-L). J Comp Neurol 1990;298:315–33.

    Article  PubMed  CAS  Google Scholar 

  14. De Zeeuw CI, Holstege JC, Ruigrok TJ, Voogd J. Ultrastructural study of the GABAergic, cerebellar, and mesodiencephalic innervation of the cat medial accessory olive: Anterograde tracing combined with immunocytochemistry. J Comp Neurol 1989; 284:12–35.

    Article  PubMed  Google Scholar 

  15. De Zeeuw CI, Ruigrok TJ, Holstege JC, Jansen HG, Voogd J. Intracellular labeling of neurons in the medial accessory olive of the cat: II. Ultrastructure of dendritic spines and their GABAergic innervation. J Comp Neurol 1990;300:478–94.

    Article  PubMed  Google Scholar 

  16. Fredette BJ, Mugnaini E. The GABAergic cerebello-olivary projection in the rat. Anat Embryol (Berl). 1991;184:225–43.

    Article  CAS  Google Scholar 

  17. Tolbert DL, Bantli H, Bloedel JR. Multiple branching of cerebellar efferent projections in cats. Exp Brain Res. 1978;31:305–16.

    Article  PubMed  CAS  Google Scholar 

  18. Svensson P, Bengtsson F, Hesslow G. Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret. Exp Brain Res. 2006;168:241–53.

    Article  PubMed  CAS  Google Scholar 

  19. Ruigrok TJ. Cerebellar nuclei: The olivary connection. Prog Brain Res. 1997;114:167–92.

    PubMed  CAS  Google Scholar 

  20. Andersson G, Oscarsson O. Climbing fiber microzones in cerebellar vermis and their projection to different groups of cells in the lateral vestibular nucleus. Exp Brain Res. 1978;32:565–79.

    PubMed  CAS  Google Scholar 

  21. Apps R, Garwicz M. Anatomical and physiological foundations of cerebellar information processing. Nature Rev: Neurosci. 2005;6:297–311.

    Article  CAS  Google Scholar 

  22. Andersson G, Hesslow G. Activity of Purkinje cells and interpositus neurones during and after periods of high frequency climbing fibre activation in the cat. Exp Brain Res. 1987;67:533–42.

    PubMed  CAS  Google Scholar 

  23. De Zeeuw CI, van Alphen AM, Hawkins RK, Ruigrok TJ. Climbing fibre collaterals contact neurons in the cerebellar nuclei that provide a GABAergic feedback to the inferior olive. Neuroscience. 1997;80:981–6.

    Article  PubMed  Google Scholar 

  24. De Zeeuw CI, Berrebi AS. Individual Purkinje cell axons terminate on both inhibitory and excitatory neurons in the cerebellar and vestibular nuclei. Ann NY Acad Sci. 1996;781:607–10.

    Article  PubMed  Google Scholar 

  25. Garifoli A, Scardilli G, Perciavalle V. Effects of cerebellar dentate nucleus GABAergic cells on rat inferior olivary neurons. Neuroreport. 2001;12:3709–13.

    Article  PubMed  CAS  Google Scholar 

  26. Andersson G, Hesslow G. Inferior olive excitability after high frequency climbing fibre activation in the cat. Exp Brain Res. 1987;67:523–32.

    PubMed  CAS  Google Scholar 

  27. Andersson G, Hesslow G. Activity of Purkinje cells and interpositus neurones during and after periods of high frequency climbing fibre activation in the cat. Exp Brain Res. 1987;67:533–42.

    PubMed  CAS  Google Scholar 

  28. Bengtsson F, Svensson P, Hesslow G. Feedback control of Purkinje cell activity by the cerebello-olivary pathway. Eur J Neurosci. 2004;20:2999–3005.

    Article  PubMed  CAS  Google Scholar 

  29. Lang EJ, Sugihara I, Llinas R. GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat. J Neurophysiol. 1996;76:255–75.

    PubMed  CAS  Google Scholar 

  30. Angaut P, Sotelo C. The dentato-olivary projection in the rat as a presumptive GABAergic link in the olivo-cerebelloolivary loop. An ultrastructural study. Neurosci Lett. 1987;83:227–31.

    Article  PubMed  CAS  Google Scholar 

  31. Angaut P, Sotelo C. Synaptology of the cerebello-olivary pathway. Double labelling with anterograde axonal tracing and GABA immunocytochemistry in the rat. Brain Res. 1989;479:361–5.

    Article  PubMed  CAS  Google Scholar 

  32. De Zeeuw CI, Ruigrok TJ. Olivary projecting neurons in the nucleus of Darkschewitsch in the cat receive excitatory monosynaptic input from the cerebellar nuclei. Brain Res. 1994;653:345–50.

    Article  PubMed  Google Scholar 

  33. Ruigrok TJ, Voogd J. Cerebellar influence on olivary excitability in the cat. Eur J Neurosci. 1995;7:679–93.

    Article  PubMed  CAS  Google Scholar 

  34. Onodera S. Olivary projections from the mesodiencephalic structures in the cat studied by means of axonal transport of horseradish peroxidase and tritiated amino acids. J Comp Neurol. 1984;227:37–49.

    Article  PubMed  CAS  Google Scholar 

  35. De Zeeuw CI, Holstege JC, Ruigrok TJ, Voogd J. Mesodiencephalic and cerebellar terminals terminate upon the same dendritic spines in the glomeruli of the cat and rat inferior olive: An ultrastructural study using a combination of [3H]leucine and wheat germ agglutinin coupled horseradish peroxidase anterograde tracing. Neuroscience. 1990;34: 645–55.

    Article  PubMed  Google Scholar 

  36. Thalmann RH, Ayala GF. A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett. 1982;29:243.

    Article  PubMed  CAS  Google Scholar 

  37. Turgeon SM, Albin RL. Postnatal ontogeny of Gaba(B) binding in rat brain. Neuroscience. 1994;62:601–13.

    Article  PubMed  CAS  Google Scholar 

  38. Mott DD, Li Q, Okazaki MM, Turner DA, Lewis DV. GABA(B)-receptor-mediated currents in interneurons of the dentate-hilus border. J Neurophysiol. 1999;82:1438–50.

    PubMed  CAS  Google Scholar 

  39. Gingrich KJ, Roberts WA, Kass RS. Dependence of the GABAA receptor gating kinetics on the alpha-subunit isoform: implications for structure-function relations and synaptic transmission. J Physiol. 1995;489:529–43.

    PubMed  CAS  Google Scholar 

  40. Devor A, Fritschy JM, Yarom Y. Spatial distribution and subunit composition of GABA(A) receptors in the inferior olivary nucleus. J Neurophysiol. 2001;85:1686–96.

    PubMed  CAS  Google Scholar 

  41. Cerminara NL, Rawson JA. Evidence that climbing fibers control an intrinsic spike generator in cerebellar Purkinje cells. J Neurosci. 2004;24:4510–17.

    Article  PubMed  CAS  Google Scholar 

  42. Hausser M, Clark BA. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron. 1997;19:665–78.

    Article  PubMed  CAS  Google Scholar 

  43. Lang EJ. Organization of olivocerebellar activity in the absence of excitatory glutamatergic input. J Neurosci. 2001;21:1663–75.

    PubMed  CAS  Google Scholar 

  44. Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000;20:9004–16.

    PubMed  CAS  Google Scholar 

  45. Colin F, Manil J, Desclin JC. The olivocerebellar system. I. Delayed and slow inhibitory effects: An overlooked salient feature of cerebellar climbing fibers. Brain Res. 1980;187:3–27.

    Article  PubMed  CAS  Google Scholar 

  46. Rawson JA, Tilokskulchai K. Suppression of simple spike discharges of cerebellar Purkinje cells by impulses in climbing fibre afferents. Neurosci Lett. 1981;25:125–30.

    Article  PubMed  CAS  Google Scholar 

  47. Montarolo PG, Palestini M, Strata P. The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat. J Physiol. 1982;332:187–202.

    PubMed  CAS  Google Scholar 

  48. Demer JL, Echelman DA, Robinson DA. Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat. Brain Res. 1985;346:22–31.

    Article  PubMed  CAS  Google Scholar 

  49. Ekerot CF, Gustavsson P, Oscarsson O, Schouenborg J. Climbing fibres projecting to cat cerebellar anterior lobe activated by cutaneous A and C fibres. J Physiol (Lond). 1987;386:529–38.

    CAS  Google Scholar 

  50. Hesslow G. Correspondence between climbing fibre input and motor output in eyeblink-related areas in cat cerebellar cortex. J Physiol (Lond). 1994;476:229–44.

    CAS  Google Scholar 

  51. Miall RC, Keating JG, Malkmus M, Thach WT. Simple spike activity predicts occurrence of complex spike cerebellar Purkinje cells. Nature Neurosci. 1998;1:13–15.

    Article  PubMed  CAS  Google Scholar 

  52. Jorntell H, Ekerot CF. Receptive field plasticity profoundly alters the cutaneous parallel fiber synaptic input to cerebellar interneurons in vivo. J Neurosci. 2003;23:9620–31.

    PubMed  Google Scholar 

  53. Sugihara I, Wu H, Shinoda Y. Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat. J Comp Neurol. 1999;414:131–48.

    Article  PubMed  CAS  Google Scholar 

  54. Hesslow G, Yeo CH. The functional anatomy of skeletal conditioning. In: Moore JW, editor. A neuroscientist’s guide to classical conditioning. New York: Springer-Verlag; 2002. pp 86–146.

    Google Scholar 

  55. Christian KM, Thompson RF. Neural substrates of eyeblink conditioning: Acquisition and retention. Learn Mem. 2003;10:427–55.

    Article  PubMed  Google Scholar 

  56. Bengtsson F. The cerebello-olivary feedback system. Ph.D. Thesis, Lund University, 2005.

  57. Sears LL, Steinmetz JE. Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response. Brain Res. 1991;545:114–22.

    Article  PubMed  CAS  Google Scholar 

  58. Hesslow G, Ivarsson M. Inhibition of the inferior olive during conditioned responses in the decerebrate ferret. Exp Brain Res. 1996; 110:36–46.

    Article  PubMed  CAS  Google Scholar 

  59. Nicholson DA, Freeman JH, Jr. Addition of inhibition in the olivocerebellar system and the ontogeny of a motor memory. Nature Neurosci. 2003;6:532–7.

    PubMed  CAS  Google Scholar 

  60. Kamin LJ. Predictability, surprise attention and conditioning. In: Campbell B, Church R, editors. Punishment and aversive behavior. New York: Appleton-Century-Crofts; 1969.

    Google Scholar 

  61. Kim JJ, Krupa DJ, Thompson RF. Inhibitory cerebelloolivary projections and blocking effect in classical conditioning. Science. 1998;279:570–3.

    Article  PubMed  CAS  Google Scholar 

  62. Medina JF, Nores WL, Mauk MD. Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature. 2002;416:330–3.

    Article  PubMed  CAS  Google Scholar 

  63. Apps R, Lee S. Gating of transmission in climbing fibre paths to cerebellar cortical C1 and C3 zones in the rostral paramedian lobule during locomotion in the cat [see comments]. J Physiol (Lond). 1999;516(Pt 3):875–83.

    Article  CAS  Google Scholar 

  64. Pardoe J, Edgley SA, Drew T, Apps R. Changes in excitability of ascending and descending inputs to cerebellar climbing fibres during locomotion. J Neurosci. 2004;24:2656–66.

    Article  PubMed  CAS  Google Scholar 

  65. Devor A. The great gate: Control of sensory information flow to the cerebellum. Cerebellum. 2002;1:27–34.

    Article  PubMed  Google Scholar 

  66. Apps R. Gating of climbing fibre input to cerebellar cortical zones. Prog Brain Res. 2000;124:201–11.

    Article  PubMed  CAS  Google Scholar 

  67. Llinas R, Baker R, Sotelo C. Electrotonic coupling between neurons in cat inferior olive. J Neurophysiol. 1974;37: 560–71.

    PubMed  CAS  Google Scholar 

  68. Sotelo C, Llinas R, Baker R. Structural study of inferior olivary nucleus of the cat: Morphological correlates of electrotonic coupling. J Neurophysiol. 1974;37:541–59.

    PubMed  CAS  Google Scholar 

  69. De Zeeuw CI, Simpson JI, Hoogenraad CC, Galjart N, Koekkoek SK, Ruigrok TJ. Microcircuitry and function of the inferior olive. Trends Neurosci. 1998;21:391–400.

    Article  PubMed  Google Scholar 

  70. Llinas R, Welsh JP. On the cerebellum and motor learning. Curr Opin Neurobiol. 1993;3:958–65.

    Article  PubMed  CAS  Google Scholar 

  71. Kistler WM, De Jeu MT, Elgersma Y, Van Der Giessen RS, Hensbroek R, Luo C, et al. Analysis of Cx36 knockout does not support tenet that olivary gap junctions are required for complex spike synchronization and normal motor performance. Ann NY Acad Sci. 2002;978:391–404.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Germund Hesslow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bengtsson, F., Hesslow, G. Cerebellar control of the inferior olive. Cerebellum 5, 7–14 (2006). https://doi.org/10.1080/14734220500462757

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/14734220500462757

Keywords

Navigation