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Tonic activation of presynaptic GABAB receptors on rat pallidosubthalamic terminals1

	author = {Lei CHEN and Wing-ho YUNG},
	title = {Tonic activation of presynaptic GABA B  receptors on rat pallidosubthalamic terminals 1 },
	journal = {Acta Pharmacologica Sinica},
	volume = {26},
	number = {1},
	year = {2016},
	keywords = {},
	abstract = {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 GABAB 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 GABAB agonist and antagonist on action potential-independent inhibitory postsynaptic currents (IPSCs), as well as holding current, were examined.
Results: Superfusion of baclofen, a GABAB receptor agonist, significantly reduced the frequency of GABAA 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 GABAB 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 GABAB receptors on the pallidosubthalamic terminals over the postsynaptic GABAB receptors on subthalamic neurons. Furthermore, the presynaptic, but not the postsynaptic, GABAB receptors are tonically active, suggesting that the presynaptic GABAB receptors in the subthalamic nucleus are potential therapeutic target for the treatment of Parkinson disease.},
	issn = {1745-7254},	url = {}