Muscarine M<SUB>2</SUB> Receptor-mediated Presynaptic Inhibition of GABAergic Transmission in Rat Meynert Neurons

Muscarine M2 Receptor-Muscarine M<SUB>2</SUB> Receptor-mediated Presynaptic Inhibition of GABAergic Transmission in Rat Meynert NeuronsPresynaptic Inhibition of GABAergic Transmission in Rat Meynert Neurons

<P> Cholinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) by the activation of muscarine receptors was investigated in mechanically dissociated rat nucleus basalis of the Meynert neurons using the conventional whole-cell patch recording configuration. Muscarine (10μM) reversibly and concentration-dependently decreased mIPSC frequency without affecting the current amplitude distribution. Muscarine action on GABAergic mIPSCs was completely blocked by 1μM methoctramine, a selective M<SUB>2</SUB> receptor antagonist, but not by 1μM pirenzepine, a selective M<SUB>1</SUB> receptor antagonist. NEM (10μM), a G-protein uncoupler, attenuated the inhibitory action of muscarine on GABAergic mIPSC frequency. Muscarine still could decrease GABAergic mIPSC frequency even in the Ca<SUP>2&#8290;</SUP>-free external solution. However, the inhibitory action of muscarine on GABAergic mIPSCs was completely occluded in the presence of forskolin. The results suggest that muscarine acts presynaptically and reduces the probability of spontaneous GABA release, and that such muscarine-induced inhibitory action seems to be mediated by G-protein-coupled M<SUB>2</SUB> receptors, via the reduction of cAMP production. Accordingly, M<SUB>2</SUB> receptor-mediated disinhibition of nBM neurons might play one of important roles in the regulation of cholinergic outputs from nBM neurons as well as the excitability of nBM neurons themselves.