High-frequency pallidal stimulation disrupts information flow through the pallidum by GABAergic inhibition

To elucidate the mechanism of deep brain stimulation (DBS) targeting the internal segment of the globus pallidus (GPi), neuronal activity of the GPi and the external segment of the globus pallidus (GPe) was examined during local electrical microstimulation in normal awake monkeys. Single-pulse stimulation of the GPi evoked brief inhibition in neighboring GPi neurons, which was mediated by GABA(A) receptors. High-frequency stimulation of the GPi completely inhibited spontaneous firings of GPi neurons by activation of GABA(A) and GABA(B) receptors. Local single-pulse stimulation directly excited some GPi neurons. Such directly evoked responses were also inhibited by high-frequency stimulation through GABA(A) receptors. In contrast to the GPi, single-pulse and high-frequency stimulation of the GPe induced complex responses composed of GABAergic inhibition and glutamatergic excitation in neighboring GPe neurons. Cortically evoked triphasic responses of GPi neurons were completely inhibited during high-frequency GPi stimulation. These findings suggest that GPi-DBS dissociates inputs and outputs in the GPi by intense GABAergic inhibition and disrupts information flow through the GPi.