Presynaptic inhibition by muscimol through GABA(B) receptors

The gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol is widely used as a tool for reducing neuronal activities particularly in experiments in vivo. At the synapse formed by the calyx of Held in the rat brainstem slice, the GABA(A) receptor agonist muscimol (> 10 mu m) attenuated the amplitude of excitatory post synaptic currents (EPSCs) accompanied by an increase in the coefficient of Variation of EPSCs, suggesting its presynaptic inhibitory effect. This muscimol effect was not affected by bicuculline but occluded the presynaptic inhibitory effect of the GABA(B) receptor agonist baclofen and was abolished by the type B GABA (GABA(B)) receptor-specific antagonist (+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 20 mu M) We conclude that muscimol activates presynaptic GABA(B) receptors thereby attenuating synaptic transmission.