A role for NMDAR-dependent cerebellar plasticity in adaptive control of saccades in humans

Background Saccade pulse amplitude adaptation is mediated by the dorsal cerebellar vermis and fastigial nucleus. Long-term depression at the parallel fibre-Purkinjie cell synapses has been suggested to provide a cellular mechanism for the corresponding learning process. The mechanisms and sites of this plasticity, however, are still debated. Objective To test the role of cerebellar plasticity phenomena on adaptive saccade control. Methods We evaluated the effect of continuous theta burst stimulation (cTBS) over the posterior vermis on saccade amplitude adaptation and spontaneous recovery of the initial response. To further identify the substrate of synaptic plasticity responsible for the observed adaptation impairment, subjects were pre-treated with memantine, an N-methyl-D-aspartate receptor (NMDAR) antagonist. Results Amplitude adaptation was altered by cTBS, suggesting that cTBS interferes with cerebellar plasticity involved in saccade adaptation. Amplitude adaptation and spontaneous recovery were not affected by cTBS when recordings were preceded by memantine administration. Conclusion The effects of cTBS are NMDAR-dependent and are likely to involve long-term potentiation or long-term depression at specific synaptic connections of the granular and molecular layer, which could effectively take part in cerebellar motor learning.