Contribution of glutamatergic projections to neurons in the nonhuman primate lateral substantia nigra pars reticulata for the reactive inhibition
The basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, most likely from the subthalamic nucleus, drive the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinsons disease.

Significance StatementUnderstanding how the basal ganglia facilitate desired actions while suppressing unwanted ones is fundamental to neuroscience. This study shows that neurons in the primate substantia nigra pars reticulata (SNr) bidirectionally modulate activity to control action, decreasing firing rates to facilitate movements and increasing rates to suppress them. Importantly, we provide causal evidence that glutamatergic inputs to the lateral SNr mediate action suppression. These findings reveal a conserved mechanism of action control in primates and highlight the role of excitatory inputs in behavioral inhibition. This advances our understanding of basal ganglia function and has significant implications for treating movement disorders like Parkinsons disease.