M3-MUSCARINIC-RECEPTORS MEDIATE CHOLINERGIC EXCITATION OF THE SPONTANEOUS ACTIVITY OF SUBTHALAMIC NEURONS IN THE RAT

The effect of the muscarinic antagonist on carbachol-induced increase in spontaneous activity of neurons of the subthalamic nucleus was exam ined by recording the extracellular unitary activity in an in vitro sl ice 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) antago nist 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP) was considerably less than the other muscarinic antagonists (M(1) antagoni st pirenzepine, IC50 1340 +/- 110 nM; M(2) antagonist AF-DX-116, IC50 6780 +/- 690 nM). These results suggest that the cholinergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action an d this effect is likely mediated via muscarinic receptor type 3.