Effects of serotonin on cerebellar Purkinje cells are dependent on the baseline firing rate

Abstract

Serotonin applied iontophoretically to cerebellar Purkinje cells elicited one of three effects: inhibition (62% of the cells), biphasic response (27%), and excitation (11%). This study describes a correlation between the spontaneous discharge rate of Purkinje cells and the action of serotonin. Purkinje neurons that responded to serotonin with an increase in firing rate had a significantly slower pre-drug firing frequency (40 Hz) than those cells that were suppressed by serotonin (51 Hz). Furthermore, it was shown that with increasing firing rates the proportion of excitations decreased, and the proportion of depressions increased. A quantitative comparison revealed a statistically significant correlation between the spontaneous discharge rate of cells displaying excitation and the magnitude of the excitatory response. On several occasions, the direction of the Purkinje cell response to serotonin reversed following a decrease or increase in the baseline spontaneous rate. Glutamate- or asparate-induced excitations elicited an augmentation of serotonin-mediated inhibition and in some cases a reversal of excitation to inhibition. Likewise, the lowering of neuronal activity by the continuous application of glycine augmented excitation and reduced and reversed serotonin inhibitions. Preliminary results from experiments in which various receptor antagonists were tested against serotonin actions suggest that the effects of serotonin occur, at least in part, at postsynaptic sites on Purkinje cells. These results strongly suggest that the overall qualitative effects of serotonin is to set Purkinje cells at a preferred firing rate. In this sense, the term biaser or modulator may best describe the role of serotonin in the cerebellum.