Modulatory role of serotonin on GABA-elicited inhibition of cerebellar Purkinje cells

Abstract

The present study was designed to directly examine the postsynaptic actions of serotonin on GABA-mediated inhibition of cerebellar Purkinje cells. The findings indicate that serotonin at currents that produced minimal effects on the spontaneous firing rates of Purkinje cells modified GABA effects in a biphasic manner. Serotonin initially decreased GABA-mediated inhibitions followed secondarily by either continued inhibition or, in the majority of cases, augmentation of GABA responses. When a comparison was made of the secondary effects of serotonin on GABA-mediated inhibition with the initial spontaneous firing rates of the Purkinje cells, the group in which serotonin augmented GABA actions had a significantly higher initial firing frequency than the group in which serotonin attenuated GABA-mediated inhibition. Furthermore, with increasing firing rates, the proportion of cells showing augmentation of GABA inhibition increased, and the proportion of cells displaying attenuation of GABA effects decreased. Serotonin affected beta-alanine-mediated inhibitions in a manner similar to that seen with GABA, whereas glycine was differentially altered. This study identifies another neuromodulatory role of serotonin on Purkinje cells in the cerebellum. Furthermore, the effects of serotonin on GABA inhibition seem to be governed by some intrinsic property of the Purkinje cell, which is apparently related to the firing rate of the cell.