Tonic activation of presynaptic GABAB receptors on rat pallidosubthalamic terminals

Abstract

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. 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. 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. 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.