Electrophysiological and pharmacological characterization of the serotonergic system on cerebellar purkinje cells
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It has been shown that serotonergic fibers distribute widely in the cerebellum. The objectives of these experiments were to evaluate the effects of serotonin on cerebellar Purkinje cells and the influence of this substance upon the glutaminergic system within the cerebellum. This study consisted of four interrelated investigations. The first evaluated the responses of Purkinje cells to iontophoretically applied serotonin alone and in combination with various serotonin antagonists. It was observed that serotonin elicited one of three different effects on Purkinje cells: inhibition, excitation, or biphasic action consisting of inhibition followed by excitation. Excitatory effects of serotonin were antagonized or attenuated by iontophoretic application of the serotonin antagonist methysergide, whereas inhibitory effects were attenuated by the application of spiperone and ketanserin. These data suggest tentatively an involvement of different receptor sites for the inhibitory and excitatory effects of serotonin on Purkinje cells. The second set of experiments were conducted to investigate the actions of the cationic inhibitors of synaptic transmission, cobalt and manganese, and thereby determine whether presynaptic mechanisms were involved in the effects of serotonin. Excitations and inhibitions mediated by serotonin were not altered significantly in the presence of these ions. These data suggest that serotonin-mediated inhibitions and excitations may occur postsynaptically. Evaluation of the effect of serotonin on Purkinje cells after treatment with 5,7-dihydroxytryptamine (5,7-DHT) was the third part of this study. Serotonin applied microiontophoretically elicited the same effects on Purkinje cells in both treated and untreated animals: inhibition, excitation, or a biphasic effect. The spontaneous firing rates of the Purkinje cells were, however, shifted to lower frequencies after treatment with 5,7-DHT. In addition, the rate dependency of the activity of serotonin disappeared in animals treated with 5, 7-DHT. These results indicate that serotonin influences the spontaneous firing rate of Purkinje cells tonically in the normal state. The last part of this study was to evaluate the interaction of serotonin with the glutaminergic system that is known to exist in the cerebellum. Microiontophoretically applied serotonin inhibited the glutamate-induced excitation of Purkinje cells consistently. In conclusion, the present study suggests that the intrinsic serotonergic system exerts a tonic influence on the spontaneous firing rates of Purkinje cells. Secondly, microiontophoretically applied serotonin affects Purkinje cell firing directly and modulates glutamate-induced excitations of Purkinje cells.