Origins of GABAA and GABAB receptor-mediated responses of globus pallidus induced after stimulation of the putamen in the monkey

The external and internal segments of the pallidum (GPe and GPi) receive heavy GABAergic innervations from the neostriatum, an input nucleus of the basal ganglia. The GPe neurons provide another major GABAergic innervation to the GPe itself and GPi. Although these GABAergic inputs are considered to play key roles in controlling the level and pattern of firing activity of pallidal neurons in both normal and pathophysiological conditions, these inputs have not been well characterized in vivo. Here, we characterized the responses of pallidal neurons to single and burst stimulation of the putamen (Put) in awake monkeys. Unit recordings in combination with local infusion of drugs and a chemical blockade of the subthalamic nucleus (STN), the major origin of excitatory afferents, revealed the following. Under STN blockade, the duration of single Put stimulation induced gabazine (a GABAA antagonist)-sensitive responses differed greatly in the GPe (similar to 400 ms long) and in the GPi (60 ms long). Burst stimulation of the Put induced CGP55845 [(2S)-3-{[(1S)-1-(3,4 dichlorophenyl)ethyl] amino-2-hydroxypropyl}(phenylmethyl) phosphinic acid] (a GABAB antagonist)- sensitive responses in the GPe and GPi. However, the data suggested that the origin of the GABAB responses was the GPe, not the Put. Local CGP55845 application increased the spontaneous firing of GPe and GPi neurons, suggesting that GABA released from the axons of GPe neurons effectively activates GABAB receptors in the GPe and GPi and contributes significantly to the control of the level of neuronal activity.