Effect of Tremorigenic Agents on the Cerebellum: A Review of Biochemical and Electrophysiological Data

Abstract

Publisher Summary On the basis of electrophysiological results and pharmacological manipulations, the chapter discusses some hypotheses of the neurophysiological and biochemical bases of the effects of tremorigenic drugs on the cerebellum. Two types of afferent excitatory neurons impinge on the cerebellar cortex: the climbing fibers, originating in the olive and synapsing directly with Purkinje cells, and the mossy fibers, synapsing with the granular cells. The axons of the granular cells generate the parallel fibers that in turn synapse with Purkinje cells; the parallel fibers, however, also impinge on numerous inhibitory neurons: stellate, basket, and Golgi cells. The activation of these inhibitory neurons may extinguish the excitation of Purkinje cells exerted through the parallel fibers. One hypothesis is that these drugs exert a presynaptic effect antagonizing inhibitory serotoninergic innervation and releasing the tendency of the olivary neurons to fire repetitively. This tendency is because of the electrotonic coupling among neurons, as indicated by electrophysiological and anatomical data (gap junctions). Through the climbing fibers, Purkinje cells are activated; the activation of Purkinje cells is accompanied by an increase of the cGMP content of the cerebellar cortex. From the cerebellar cortex through the cerebellar and reticular nuclei rhythmic stimuli reach the spinal motoneurons for the final motor issue.