Opposing functions of glutamatergic inputs between the globus pallidus external segment and substantia nigra pars reticulata

Summary The indirect pathway of the basal ganglia, including the subthalamic nucleus (STN) and globus pallidus external segment (GPe), is believed to play a crucial role in suppressing involuntary movements. However, recent evidence suggests the STN and GPe also facilitate voluntary movements. This study hypothesized that excitatory inputs from the STN to the GPe contribute to this facilitation, and that excitatory projections to the substantia nigra pars reticulata (SNr) are involved in the inhibition. To disrupt the STN-GPe or STN-SNr projections in monkeys during choice and fixation tasks, glutamate receptor inhibitors were injected into the GPe or SNr, which induced delayed saccade latencies toward good choices in the choice task (GPe) and caused frequent reflexive saccades to objects in the fixation task (SNr). Our findings suggest excitatory inputs to the GPe and SNr work in opposing manners, providing new insights that redefine our understanding of the functions of basal ganglia pathways. Highlights STN and GPe neuronal activity increased when good objects were chosen SNr activity increased when rejecting bad objects and decreased when accepting good objects Excitatory inputs inactivation in the GPe caused delayed saccade to good objects Excitatory projection inhibition to the SNr suppressed involuntary saccade control