GPE

GPe stands for the external segment of the globus pallidus, a subcortical structure within the basal ganglia of the mammalian brain. It lies lateral to the internal segment (GPi) and is composed predominantly of GABAergic neurons. Two principal neuron types have been described: prototypical neurons that project mainly to the subthalamic nucleus and output nuclei, and arkypallidal neurons that project back to the striatum.

The external segment receives inhibitory inputs from the striatum via the indirect pathway and excitatory inputs from the subthalamic nucleus. It also receives modulatory dopaminergic input from the substantia nigra pars compacta. The GPe then sends inhibitory outputs to the subthalamic nucleus and to the GPi/SNr, and, via arkypallidal neurons, back to the striatum. Unlike some components of the basal ganglia, the GPe does not project directly to the thalamus.

Functionally, the GPe modulates activity within the indirect pathway and helps regulate motor control by shaping the overall output of the basal ganglia circuitry. It participates in the generation and coordination of motor commands and in the timing of movement-related activity, contributing to the fine-tuning of movement.

Clinical relevance is notable in movement disorders. In Parkinson’s disease, dopaminergic loss alters GPe firing and the balance of indirect pathway signaling, contributing to motor symptoms and network hypersynchrony with the subthalamic nucleus. Deep brain stimulation and other therapies targeting basal ganglia circuits often involve the GPi or STN, but the GPe is also a focus of ongoing research as a potential intervention point. In Huntington’s disease, GPe dysfunction contributes to dyskinetic movements.