Summary
Purkinje cells were recorded extracellularly and mapped in the cerebellar cortex of the rat under tremogenic doses of harmaline. Four différent types of responses were encountered, of which two were considered as being responsible for the harmaline tremor. The latter had a regular firing pattern of complex spikes at 5 to 10 Hz and were mostly found in the vermis. Their number decreased in the more lateral region of the cerebellar cortex until they eventually disappeared. Horseradish peroxidase was injected into all the areas of the cerebellar cortex containing Purkinje cells with harmaline-induced activity. Labeled neurons were in all cases traced to the medial accessory olive. The metabolic activity of the inferior olive under harmaline was measured with 2-deoxyglucose. Increased labeling was only found in the medial accessory olive. Such an increase was demonstrated as being due to a direct effect of the drug on the inferior olivary neurons, indicating that the medial accessory olive is responsible for the harmaline tremor in the rat. Our results point out that, in the rat, there is an inverse relationship between serotoninergic innervation of a region in the inferior olivary nucleus and that with harmaline sensitivity, therefore a serotoninergic mechanism hypothesis for the harmaline tremor needs further investigation.
Similar content being viewed by others
References
Agarwal SL, Bose D (1967) A study of the role of brain catecholamine in drug induced tremor. Br J Pharmacol Chemother 30: 349–353
Ahmed A, Taylor NRW (1959) The analysis of drug tremor in mice. Brit J Pharmacol 14: 350–354
Armstrong DM (1974) Functional significance of connections of the inferior olive. Physiol Rev 54: 358–417
Armstrong DM, Harvey RJ, Schild RF (1971) Distribution in the anterior lobe of the cerebellum of branches from climbing fibres to the paramedian lobule. Brain Res 25: 203–206
Bardin JM, Batini C, Billard JM, Buisseret-Delmas C, Conrath-Verrier M, Corvaja N (1983) Cerebellar output regulation by the climbing and mossy fibers with and without the inferior olive. J Comp Neurol 213: 464–477
Batini C, Buisseret-Delmas C, Conrath-Verrier M (1979) Olivocerebellar activity during harmaline-induced tremor. A 2-(14C) deoxyglucose study. Neurosci Lett 12: 241–246
Batini C, Buisseret-Delmas C, Conrath-Verrier M (1981a) Harmaline induced tremor. I. Regional metabolic activity as revealed by 14C-2-deoxyglucose in cat. Exp Brain Res 42: 371–382
Batini C, Bernard JF, Buisseret-Delmas C, Conrath-Verrier M, Horcholle-Bossavit G (1981b) Harmaline induced tremor. II. Unit activity correlation in the interposito-rubral and in the oculomotor system of the cat. Exp Brain Res 42: 383–391
Batini C, Bernard JF, Buisseret-Delmas C, Horcholle-Bossavit G (1983) Cerebellar output response to afferent stimulation: energy consumption and unit activity in cat fastigial nucleus. Exp Brain Res 52: 400–410
Bernard JF (1983) Le tremblement harmalinique: topographie de l'activité au niveau du cortex cérébelleux chez le rat. CR Acad Sci Paris 297: 225–228
Bernard JF, Horcholle-Bossavit G (1981) Origine spinale des activités rythmiques induites par l'harmaline dans le noyau réticulaire latéral. CR Acad Sci Paris 292: 573–575
Bernard JF, Horcholle-Bossavit G (1983) Harmaline-induced rhythm in the lateral reticular nucleus. Arch Ital Biol 121: 139–150
Brodal A (1940) Experimentelle Untersuchungen über die olivocerebellare Lokalisation. Z Ges Neurol Psychiat 169: 1–153
Brodal A, Kawamura K (1980) Olivocerebellar projection: a review. Adv Anat 64: 1–140
Brodal A, Walberg F, Blackstad T (1950) Termination of spinal afferents to inferior olive in cat. J Neurophysiol 13: 431–454
Brown PA (1980) The inferior olivary connections to the cerebellum in the rat studied by retrograde axonal transport of horseradish peroxidase. Brain Res Bull 5: 267–275
Campbell NC, Armstrong DM (1983a) The olivocerebellar projection in the rat: an autoradiographic study. Brain Res 275: 215–233
Campbell NC, Armstrong DM (1983b) Topographical localization in the olivocerebellar projection in the rat: an autoradiographic study. Brain Res 275: 235–249
De Montigny C, Lamarre Y (1973) Rhythmic activity induced by harmaline in the olivo-cerebello-bulbar system of the cat. Brain Res 53: 81–95
De Montigny C, Lamarre Y (1975) Effects produced by local application of harmaline in the inferior olive. Can J Physiol Pharmacol 53: 845–849
Eisenman LM (1981) Pontocerebellar projections to the pyramis and copula pyramidis in the rat: evidence for a mediolateral topography. J Comp Neurol 199: 77–86
Groenewegen MJ, Voogd J, Freeman SL (1979) The parasagittal zonation within the olivocerebellar projection. II. Climbing fibres distribution in the intermediate and hemispheric parts of cat cerebellum. J Comp Neurol 183: 551–602
Gunn JA (1935) Relations between chemical constitution, pharmacological actions, and therapeutic uses, in the harmaline group of alkaloids. Arch Int Pharmacodyn 50: 379–396
Gwyn DG, Nicholson GP, Flumerfelt BA (1977) The inferior olivary nucleus in the rat: a light and electron microscopic study. J Comp Neurol 174: 489–520
Hara S (1953) Pharmacological studies in the function of the extrapyramidal system. Jpn J Pharmacol 2: 127–138
Headley PM, Lodge D, Duggan AW (1976) Drug induced rhythmical activity in the inferior olivary complex of the rat. Brain Res 101: 461–478
Hoddevik GH, Brodal A (1976) The olivocerebellar projection in the cat studies with the method of retrograde axonal transport of horseradish peroxidase. III. The projection to the vermal visual area. J Comp Neurol 169: 155–170
Kawamura K, Hashikawa T (1979) Olivocerebellar projections in the cat studied by means of anterograde axonal transport of labeled amino acids as tracers. Neuroscience 4: 1615–1633
Kotchabhakdi N, Walberg F, Brodal A (1978) The olivocerebellar projection in the cat studies with the method of retrograde axonal transport of horseradish peroxidase. VII. The projection to lobules simplex, Crus I and II. J Comp Neurol 182: 293–314
Lamarre Y, De Montigny C, Dumont M, Weiss M (1971) Harmaline-induced rhythmic activity of cerebellar and lower brain stem neurons. Brain Res 32: 246–250
Lamarre Y, Dumont M (1972) Activity of cerebellar and lower brain stem neurons in monkeys with harmaline-induced tremor. Medical Primatology. Proc. 3rd Conf. Exp Med Surg Primates, Lyon 1972, Part II. Karger, Basel, pp 274–281
Lamarre Y, Mercier A (1971) Neurophysiological studies of harmaline induced tremor in the cat. Can J Physiol Pharmacol 49: 1049–1058
Lamarre Y, Mercier A (1972) Etude neurophysiologique du tremblement à l'harmaline chez le chat. Rev Can Biol 31: 181–191
Lamarre Y, Weiss M (1973) Harmaline induced rhythmic activity of alpha and gamma motoneurons in the cat. Brain Res 63: 430–434
Larsell O (1952) The morphogenesis and adult pattern of the lobules and fissures of the cerebellum of the white rat. J Comp Neurol 97: 281–356
Llinás R, Volkind RA (1973) The olivo-cerebellar system: functional properties as revealed by harmaline-induced tremor. Exp Brain Res 18: 69–87
Mariani J, Delhaye-Bouchaud N (1978) Effect of diazepam on the spontaneous and harmaline induced electrical activity of Purkinje cells in the cerebellum of the rat and rabbit. Neuropharmacology 17: 45–51
Meibach RC, Glick SD, Ross DA, Cox RD, Maayani S (1980) Intraperitoneal administration and other modification of the 2-deoxyglucose-D-glucose technique. Brain Res 185: 167–176
Menétrey D, Chaouch A, Binder D, Besson JM (1982) The origin of the spinomesencephalic tract in the rat: an anatomical study using the retrograde transport of horseradish peroxidase. J Comp Neurol 206: 193–207
Mesulam MM (1976) The blue reaction product in horseradish peroxidase neurohistochemistry: incubation parameters and visibility. J Histochem Cytochem 26: 1273–1280
Mesulam MM (1978) Tetramethyl benzidine for horseradish peroxidase neurochemistry. A non carcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents. J Histochem Cytochem 26: 106–117
Pellet J, Tardy MF, Harlay F, Dubrocard S, Gilhodes JC (1974) Activités spontanées des cellules de Purkinje chez le chat chronique: etude statistique des spikes complexes. Brain Res 81: 75–95
Sjölund B, Bjorklund A, Wiklund L (1977) The indolaminergic innervation of the inferior olive. 2. Relation to harmaline induced tremor. Brain Res 131: 23–37
Sokoloff L (1975) Influence of functional activity on local cerebral glucose utilisation. In: Inguar DH, Lassen NA (eds) Brain work. The coupling of function, metabolism and blood flow in the brain. Copenhagen, Munksgaard, pp 385–388
Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shmohara M (1977) The (14C)-deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916
Swenson RS, Castro AJ (1983) The afferent connections of the inferior olivary complex in rats. An anterograde study using autoradiographic and axonal degeneration techniques. Neuroscience 8: 259–275
Weiss M (1978) Influence du système olivo-cérébello-bulbaire sur les neurones moteurs de la moelle lombaire chez le chat après administration d'harmaline. Arch Ital Biol 116: 1–15
Weiss M, Pellet J (1979) Effet de la stimulation juxtafastigiale sur l'activité rythmique des cellules de Purkinje chez le rat sous harmaline. J Neurol Sci 41: 271–286
Wiklund L, Bjorklund A, Sjölund B (1977) The indolaminergic innervation of the inferior olive. 1. Convergence with the direct spinal afferents in the areas projecting to the cerebellar anterior lobe. Brain Res 131: 1–21
Author information
Authors and Affiliations
Additional information
Assistant from University Paris VII
Rights and permissions
About this article
Cite this article
Bernard, J.F., Buisseret-Delmas, C., Compoint, C. et al. Harmaline induced tremor III. A combined simple units, horseradish peroxidase, and 2-deoxyglucose study of the olivocerebellar system in the rat. Exp Brain Res 57, 128–137 (1984). https://doi.org/10.1007/BF00231139
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00231139