Tonic activation of presynaptic GABA_B receptors on rat pallidosubthalamic terminals

Aim: The subthalamic nucleus plays a critical role in the regulation of movement, and abnormal activity of its neurons is associated with some basal ganglia motor symptoms. We examined the presence of functional presynaptic GABA_B receptors on pallidosubthalamic terminals and tested whether they were tonically active in the in vitro subthalamic slices. Methods: Whole-cell patch-clamp recordings were applied to acutely prepared rat subthalamic nucleus slices. The effects of specific GABA_B agonist and antagonist on action potential-independent inhibitory postsynaptic currents (IPSCs), as well as holding current, were examined. Results: Superfusion of baclofen, a GABA_B receptor agonist, significantly reduced the frequency of GABA_A receptor-mediated miniature IPSCs (mIPSCs), in a Cd²⁺-sensitive manner, with no effect on the amplitude, indicating presynaptic inhibition on GABA release. In addition, baclofen induced a weak outward current only in a minority of subthalamic neurons. Both the pre- and post-synaptic effects of baclofen were prevented by the specific GABA _B receptor antagonist, CGP55845. Furthermore, CGP55845 alone increased the frequency of mIPSCs, but had no effect on the holding current. Conclusion: These findings suggest the functional dominance of presynaptic GABA_B receptors on the pallidosubthalamic terminals over the postsynaptic GABA_B receptors on subthalamic neurons. Furthermore, the presynaptic, but not the postsynaptic, GABA_B receptors are tonically active, suggesting that the presynaptic GABA_B receptors in the subthalamic nucleus are potential therapeutic target for the treatment of Parkinson disease.