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The olivo-cerebellar system: Functional properties as revealed by harmaline-induced tremor

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Summary

Intracellular recording from Purkinje cells in cat cerebellar cortex demonstrated an 8–10/sec burst activity following intravenous administration of harmaline (10 mg/kg), a drug known to produce tremor at the same frequency. The burst activation of Purkinje cells was generated by large all-or-none depolarizations similar to climbing fiber (CF) excitatory postsynaptic potentials (EPSPs). Polarization of the cell membrane through the recording electrode (via a Wheatstone bridge) revealed that the all-or-none depolarization had an equilibrium potential and time course identical to the electrically evoked CF-EPSP, demonstrating directly that tremor is associated with specific activation of the CF afferent system.

Interspike frequency histograms of the burst responses of Purkinje cells show that the rhythmic CF activity may continue for several hours with approximately 10% frequency scatter, the actual frequency depending on the level of anesthesia. Simultaneous extracellular recordings from Purkinje cells near the midline vermis indicated that CFs projecting to this area fire in a synchronous manner, while simultaneous recording from three Purkinje cells at different lateralities from the midline showed that the rhythmic activity is reduced in the lateral vermis and may be absent in the cerebellar hemispheres.

Intra- and extracellular recordings from cerebellar nuclear cells (fastigial) disclosed a bursting type of activation following harmaline; a similar type of activity could be recorded in the reticular formation neurons and at inferior olive level. At spinal cord level, harmaline induced a repetitive and rhythmic activation of motoneurons which was not modified by dorsal root section. Cooling of the cerebellar cortex produced a definite desynchronization of the rhythmic motoneuronal firing. However, the basic 10/sec firing of the spinal cord motoneurons could still be observed. Following lesion of the inferior peduncles which interrupted the olivo-cerebellar pathway, the rhythmic activation of Purkinje cells, nuclear cells, vestibular and reticular cells and motoneurons disappeared. However, the rhythmic activity was maintained at inferior olivary level. It is suggested that harmaline acts directly on the inferior olive since in animals with low decerebration, cerebellectomy and spinal transection, rhythmic activity of the inferior olive could still be observed.

The results of these experiments strongly suggest that the inferior olive is able to generate the activation of motoneurons and that such influence can only take place through the activation of the cerebellar nuclei. Possible functions of the inferior olive as a generator of fast muscular transients are discussed.

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Llinás, R., Volkind, R.A. The olivo-cerebellar system: Functional properties as revealed by harmaline-induced tremor. Exp Brain Res 18, 69–87 (1973). https://doi.org/10.1007/BF00236557

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