The globus pallidus (GP) contains abundant GABAergic synapses and GABAB receptors. To investigate whether synaptically released GABA can activate pre- and postsynaptic GABAB receptors in the GP, physiological recordings were performed using rat brain slice preparations. Cell-attached recordings from GABAA antagonist-treated preparations revealed that repetitive local stimulation induced a GABAB antagonist-sensitive pause in spontaneous firings of GP neurons. Whole cell recordings revealed that the repetitive stimulation evoked fast excitatory postsynaptic potentials followed by a slow inhibitory postsynaptic potential (IPSP) in GP neurons. The slow IPSP was insensitive to a GABAA receptor antagonist, increased in amplitude with the application of ionotropic glutamate receptor antagonists, and was suppressed by the GABAB antagonist CGP55845 . The reversal potential of the slow IPSP was close to the potassium equilibrium potential. These results suggest that synaptically released GABA activated postsynaptic GABAB receptors and induced the pause and the slow IPSP. On the other hand, in the neurons that were treated to block postsynaptic GABAB responses, CGP55845 increased the amplitudes of repetitive local stimulation-induced GABAA-mediated inhibitory postsynaptic currents (IPSCs) but not the ionotropic glutamate-mediated excitatory postsynaptic currents. Moreover, the GABAB receptor specific agonist baclofen reduced the frequency of miniature IPSCs without altering their amplitude distributions. These results suggest that synaptically released GABA also activated presynaptic GABAB autoreceptors, resulting in decreased GABA release in the GP. Together, we infer that both pre- and postsynaptic GABAB receptors may play crucial roles in the control of GP neuronal activity.
