Effects of GABAergic and Glutamatergic Inputs on Temporal Prediction Signals in the Primate Cerebellar Nucleus

The cerebellum has been shown to be involved in temporal information processing. We recently demonstrated that neurons in the cerebellar dentate nucleus exhibited periodic activity predicting stimulus timing when monkeys attempted to detect a single omission of isochronous repetitive visual stimulus. In this study, we assessed the relative contribution of signals from Purkinje cells and mossy and climbing fibers to the periodic activity by comparing single neuronal firing before and during local infusion of GABA or glutamate receptor antagonists (gabazine or a mixture of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide hydrate (NBQX) and (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP)). Gabazine application reduced the magnitude of periodic activity and increased the baseline firing rate in most neurons. In contrast, during the blockade of glutamate receptors, both the magnitude of periodic firing modulation and the baseline activity remained unchanged in the population, while a minority of neurons significantly altered their activity. Furthermore, the amounts of changes in the baseline activity and the magnitude of periodic activity were inversely correlated in the gabazine experiments but not in the NBQX + CPP experiments. We also found that the variation of baseline activity decreased during gabazine application but sometimes increased during the blockade of glutamate receptors. These changes were not observed during prolonged recording without drug administration. These results suggest that the predictive neuronal activity in the dentate nucleus may mainly attribute to the inputs from the cerebellar cortex, while the signals from both mossy fibers and Purkinje cells may play a role in setting the level and variance of baseline activity during the task.