GABA-A Inhibition Shapes the Spatial and Temporal Response Properties of Purkinje Cells in the Macaque Cerebellum

Abstract

Data from in vitro and anesthetized preparations indicate that inhibition plays a major role in cerebellar cortex function. We investigated the role of GABA-A inhibition in the macaque cerebellar ventral-paraflocculus while animals performed oculomotor behaviors that are known to engage the circuit. We recorded Purkinje cell responses to these behaviors with and without application of gabazine, a GABA-A receptor antagonist, near the recorded neuron. Gabazine increased the neuronal responsiveness to saccades in all directions and the neuronal gain to VOR cancellation and pursuit, most significantly the eye and head velocity sensitivity. L-glutamate application indicated that these changes were not the consequence of increases in baseline firing rate. Importantly, gabazine did not affect behavior or efference copy, suggesting that only local computations were disrupted. Our data, collected while the cerebellum performs behaviorally relevant computations, indicate that inhibition is a potent regulatory mechanism for the control of input-output gain and spatial tuning in the cerebellar cortex.