Abstract
Stimulation around the superior cerebellar peduncle or within the deep cerebellar nuclei is known to inhibit the inferior olive with a very long latency. It has been suggested that this inhibition is mediated by the GABA-ergic nucleo-olivary pathway, but alternative explanations such as activation of an indirect excitatory pathway or a pathway via the red nucleus are possible. A long-latency inhibition via the nucleo-olivary pathway would have profound implications for cerebellar function and the present study was performed to test alternative explanations and to characterize the nucleo-olivary inhibition. Climbing fibre responses (CFRs), evoked by periorbital stimulation and recorded from the cerebellar cortex, could be inhibited by stimulation of two distinct mesencephalic areas. One was located within the superior cerebellar peduncle and the other about 1 mm further ventrally. Inhibition evoked from either area occurred in the inferior olive and was independent of a red nucleus relay. Single Purkinje cell recordings revealed that inhibition from the ventral area was not secondary to olivary activation. It is concluded that stimulation of the ventral area activated nucleo-olivary fibres. The inhibition elicited by stimulation within the peduncle probably resulted from indirect activation on the nucleo-olivary fibres via antidromic activation of the interpositus nucleus. The time courses of the inhibition from the two areas were indistinguishable. The duration of the strongest inhibition was short and had a sharp peak at about 30 ms. It is suggested that the time course of the inhibition is important for temporal regulation of learned responses.
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References
Albus J (1971) A theory of cerebellar function. Math Biosci 10:25–61
Andersson G (1984) Mutual inhibition between olivary cell groups projecting to different cerebellar microzones in the cat. Exp Brain Res 54:293–303
Andersson G, Hesslow G (1987) Activity of Purkinje cells and interpositus neurones during and after periods of high frequency climbing fibre activation in the cat. Exp Brain Res 67:533–542
Andersson G, Garwicz M, Hesslow G (1988) Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat. Exp Brain Res 72:450–456
Angaut P, Sotelo C (1987) The dentato-olivary projection in the rat as a presumptive GABAergic link in the olivo-cerebello-olivary loop. An ultrastructural study. Neurosci Lett 83:227–231
Angaut P, Sotelo C (1989) Synaptology of the cerebello-olivary pathway. Double labelling with anterograde axonal tracing and GABA immunocytochemistry in the rat. Brain Res 479:361–365
Armstrong DM (1990) Topographical localisation in the projections from the inferior olive to the paravermal cortex of the anterior lobe and paramedian lobule in the cerebellum of the cat. A brief review. Arch Ital Biol 128:183–207
Armstrong DM, Harvey RJ (1968) Responses to a spino-olivo-cerebellar pathway in the cat. J Physiol (Lond) 194:147–168
Armstrong DM, Eccles JC, Harvey RJ, Matthews PB (1968) Responses in the dorsal accessory olive of the cat to stimulation of hind limb afferents. J Physiol (Lond) 194:125–145
Ban M, Ohno T (1977) Projection of cerebellar nuclear neurones to the inferior olive by descending collaterals of ascending fibres. Brain Res 133:156–161
Bengtsson F, Svensson P, Hesslow G (2004) Feedback control of purkinje cell activity by the cerebello-olivary pathway. Eur J Neurosci 20(11):2999–3005
Cerminara NL, Rawson JA (2004) Evidence that climbing fibers control an intrinsic spike generator in cerebellar Purkinje cells. J Neurosci 24:4510–4517
Christian KM, Thompson RF (2003) Neural substrates of eyeblink conditioning: acquisition and retention. Learn Mem 10:427–455
Colin F, Manil J, Desclin JC (1980) The olivocerebellar system. I. Delayed and slow inhibitory effects: an overlooked salient feature of cerebellar climbing fibers. Brain Res 187:3–27
Davis KD, Dostrovsky JO (1986) Modulatory influences of red nucleus stimulation on the somatosensory responses of cat trigeminal subnucleus oralis neurons. Exp Neurol 91:80–101
De Zeeuw CI, Holstege JC, Calkoen F, Ruigrok TJ, Voogd J (1988) A new combination of WGA-HRP anterograde tracing and GABA immunocytochemistry applied to afferents of the cat inferior olive at the ultrastructural level. Brain Res 447:369–375
De Zeeuw CI, Holstege JC, Ruigrok TJ, Voogd J (1989) Ultrastructural study of the GABAergic, cerebellar, and mesodiencephalic innervation of the cat medial accessory olive: anterograde tracing combined with immunocytochemistry. J Comp Neurol 284:12–35
Demer JL, Echelman DA, Robinson DA (1985) Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat. Brain Res 346:22–31
Devor A, Yarom Y (2000) GABAergic modulation of olivary oscillations. Prog Brain Res 124:213–220
Devor A, Fritschy JM, Yarom Y (2001) Spatial distribution and subunit composition of GABA(A) receptors in the inferior olivary nucleus. J Neurophysiol 85:1686–1696
Dietrichs E, Walberg F (1981) The cerebellar nucleo-olivary projection in the cat. Anat Embryol (Berl) 162:51–67
Dietrichs E, Walberg F (1986) The cerebellar nucleo-olivary and olivocerebellar nuclear projections in the cat as studied with anterograde and retrograde transport in the same animal after implantation of crystalline WGA-HRP. III. The interposed nuclei. Brain Res 373:373–383
Garifoli A, Scardilli G, Perciavalle V (2001) Effects of cerebellar dentate nucleus GABAergic cells on rat inferior olivary neurons. Neuroreport 12:3709–3713
Garwicz M (1997) Sagittal zonal organization of climbing fibre input to the cerebellar anterior lobe of the ferret. Exp Brain Res 117:389–398
Gellman R, Houk JC, Gibson AR (1983) Somatosensory properties of the inferior olive of the cat. J Comp Neurol 215:228–243
Gingrich KJ, Roberts WA, Kass RS (1995) Dependence of the GABAA receptor gating kinetics on the alpha-subunit isoform: implications for structure-function relations and synaptic transmission. J Physiol 489:529–543
Graybiel AM, Nauta HJ, Lasek RJ, Nauta WJ (1973) A cerebello-olivary pathway in the cat: an experimental study using autoradiographic tracing technics. Brain Res 58:205–211
Hesslow G (1986) Inhibition of inferior olivary transmission by mesencephalic stimulation in the cat. Neurosci Lett 63:76–80
Hesslow G (1994) Correspondence between climbing fibre input and motor output in eyeblink-related areas in cat cerebellar cortex. J Physiol (Lond) 476:229–244
Hesslow G, Ivarsson M (1996) Inhibition of the inferior olive during conditioned responses in the decerebrate ferret. Exp Brain Res 110:36–46
Hesslow G, Yeo CH (2002) The functional anatomy of skeletal conditioning. In: Moore JW (ed) A neuroscientist’s guide to classical conditioning. Springer, New York, pp 86–146
Hesslow G, Svensson P, Ivarsson M (1999) Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents. Neuron 24:179–185
Horn KM, Hamm TM, Gibson AR (1998) Red nucleus stimulation inhibits within the inferior olive. J Neurophysiol 80:3127–3136
Ito M (1984) The cerebellum and neuronal control. Raven, New York
Ito M (1989) Long-term depression. Annu Rev Neurosci 12:85–102
Ivarsson M, Hesslow G (1993) Bilateral control of the orbicularis oculi muscle by one cerebellar hemisphere in the ferret. Neuroreport 4:1127–1130
Kim JJ, Krupa DJ, Thompson RF (1998) Inhibitory cerebello-olivary projections and blocking effect in classical conditioning. Science 279:570–573
Lang EJ, Sugihara I, Llinas R (1996) GABAergic modulation of complex spike activity by the cerebellar nucleoolivary pathway in rat. J Neurophysiol 76:255–275
Legendre A, Courville J (1987) Origin and trajectory of the cerebello-olivary projection: an experimental study with radioactive and fluorescent tracers in the cat. Neuroscience 21:877–891
Linden DJ, Connor JA (1995) Long-term synaptic depression. Annu Rev Neurosci 18:319–357
Llinas R, Yarom Y (1981) Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol (Lond) 315:569–584
Llinas R, Yarom Y (1986) Oscillatory properties of guinea-pig inferior olivary neurones and their pharmacological modulation: an in vitro study. J Physiol 376:163–182
Llinas R, Baker R, Sotelo C (1974) Electrotonic coupling between neurons in cat inferior olive. J Neurophysiol 37:560–571
Martin GF, Henkel CK, King JS (1976) Cerebello-olivary fibers: their origin, course and distribution in the North American opossum. Exp Brain Res 24:219–236
Montarolo PG, Palestini M, Strata P (1982) The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat. J Physiol (Lond) 332:187–202
Mott DD, Li Q, Okazaki MM, Turner DA, Lewis DV (1999) GABA(B)-receptor-mediated currents in interneurons of the dentate-hilus border. J Neurophysiol 82:1438–1450
Nelson B, Mugnaini E (1989) Origins of GABA-ergic inputs to the inferior olive. In: Strata P (eds) The olivocerebellar system in motor control. Springer Berlin Heidelberg New York pp 86–107
Oscarsson O (1980) Functional organisation of olivary projection to the cerebellar anterior lobe. In: Courville J, de Montigny C, Lamarre Y (eds) The inferior olivary nucleus: anatomy and physiology. Raven, New York, pp 279–289
Rawson JA, Tilokskulchai K (1981) Suppression of simple spike discharges of cerebellar Purkinje cells by impulses in climbing fibre afferents. Neurosci Lett 25:125–130
Ruigrok TJ (1997) Cerebellar nuclei: the olivary connection. Prog Brain Res 114:167–192
Ruigrok TJ, Voogd J (1995) Cerebellar influence on olivary excitability in the cat. Eur J Neurosci 7:679–693
Savio T, Tempia F (1985) On the Purkinje cell activity increase induced by suppression of inferior olive activity. Exp Brain Res 57:456–463
Sears LL, Steinmetz JE (1991) Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response. Brain Res 545:114–122
Sotelo C, Gotow T, Wassef M (1986) Localization of glutamic-acid-decarboxylase-immunoreactive axon terminals in the inferior olive of the rat, with special emphasis on anatomical relations between GABAergic synapses and dendrodendritic gap junctions. J Comp Neurol 252:32–50
Thalmann RH, Ayala GF (1982) A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett 29:243
Thompson RF, Krupa DJ (1994) Organization of memory traces in the mammalian brain. Annu Rev Neurosci 17:519–549
Tolbert DL, Massopust LC, Murphy MG, Young PA (1976) The anatomical organization of the cerebello-olivary projection in the cat. J Comp Neurol 170:525–544
Tolbert DL, Bantli H, Bloedel JR (1978) Multiple branching of cerebellar efferent projections in cats. Exp Brain Res 31:305–316
Turgeon SM, Albin RL (1994) Postnatal ontogeny of gaba(b) binding in rat-brain. Neuroscience 62:601–613
Weiss C, Houk JC, Gibson AR (1990) Inhibition of sensory responses of cat inferior olive neurons produced by stimulation of red nucleus. J Neurophysiol 64:1170–1185
Yeo CH, Hesslow G (1998) Cerebellum and conditioned reflexes. Trends Cogn Sci 2:322–330
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This work was supported by grants from the Swedish Research Council (09899), the Segerfalk Foundation and the Knut and Alice Wallenberg Foundation.
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Svensson, P., Bengtsson, F. & Hesslow, G. Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret. Exp Brain Res 168, 241–253 (2006). https://doi.org/10.1007/s00221-005-0086-y
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DOI: https://doi.org/10.1007/s00221-005-0086-y