TY - JOUR T1 - Muscarine induces an anomalous inhibition of synaptic transmission in rat auditory thalamic neurons in vitro. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 838 LP - 844 VL - 275 IS - 2 AU - D M Mooney AU - B Hu AU - V V Senatorov Y1 - 1995/11/01 UR - http://jpet.aspetjournals.org/content/275/2/838.abstract N2 - Muscarinic receptor-mediated inhibition of central synaptic transmission was studied in a monosynaptic pathway connecting the inferior colliculus and the auditory thalamus in in vitro rat brain explants. Extra- and intracellular synaptic responses were recorded by sharp electrode and whole-cell patch clamp techniques in the ventral nucleus of the medial geniculate body after electrical stimulation of the brachium of the inferior colliculus. Stimulation of tectal afferents evoked either a high-frequency burst or a single-spike synaptic response in ventral geniculate neurons. Bath application of muscarinic receptor agonists abolished responses consisting of a high-frequency burst, but not responses consisting of a single spike. In the majority of single-spike cells muscarinic agonists often induced a synaptic facilitation. The burst blocking effect was mimicked by a moderate elevation of extracellular potassium. Intracellular recordings showed that the burst synaptic responses similar to that recorded extracellularly were induced by an excitatory postsynaptic potential. This synaptic potential, by first activating a low-threshold spike, was able to evoke a burst of sodium spike discharges. Muscarinic agonists caused a slow membrane depolarization that inactivated the low-threshold spike, leading to a blockade of the burst response. This mechanism is tentatively termed here as EPSP-LTS decoupling. Our results therefore support the hypothesis that part of the muscarinic receptor-mediated synaptic inhibition previously reported in anesthetized animal preparations in vivo represents a membrane depolarization rather than pre- or postsynaptic inhibition. ER -