M3 muscarinic receptors mediate cholinergic excitation of the spontaneous activity of subthalamic neurons in the rat

Abstract

The effect of the muscarinic antagonist on carbachol-induced increase in spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. Carbachol produced (98% of the 263 neurons tested) an increase (twofold of the basal at 500 nM) of the discharge frequency. The EC 50 for the carbachol-induced effect was 375 ± 8.7 nM (mean ± SEM). The response was blocked by muscarinic antagonists in a dose dependent manner. However, the IC50 (94 ± 3 nM) for the M 3 antagonist 4-diphenyl acetoxy- N-methyl piperidine methobromide (4-DAMP) was considerably less than the other muscarinic antagonists (M 1 antagonist pirenzepine, IC 50 1340 ± 110 nM; M 2 antagonist AF-DX-116, IC 50 6780 ± 690 nM). These results suggest that the cholinergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action and this effect is likely mediated via muscarinic receptor type 3.