Sound sequence discrimination learning is dependent on cholinergic inputs to the rat auditory cortex

In rat auditory cortex (AC) slices, synaptic potentiation following heterosynaptic stimulation is affected by the stimulus sequence used for induction. It was hypothesized that this sequence-dependent plasticity might be partly involved in the cellular mechanisms underlying sound sequence discrimination. Sequence dependence is abolished by muscarinic receptor antagonists. Therefore, dependence of sound sequence discrimination learning on cholinergic inputs to the rat AC was investigated. Rats were trained to discriminate the sequences of two sound components and a licking behavior in response to one of two possible sequences was rewarded with water. Atropine, a muscarinic receptor antagonist, attenuated sound sequence discrimination learning. The acquired sound sequence discrimination was not affected by atropine. Injections of the cholinergic immunotoxin 192IgG-saporin into the AC suppressed sound sequence discrimination learning, while discrimination between the two sound components was not affected. An inhibitor of M-current, linopirdine, restores the sequence dependence of synaptic potentiation in the AC slices suppressed by atropine. In this study, sound sequence discrimination learning attenuated by 192IgG-saporin was also restored by linopirdine. These similarities between sequence dependent plasticity in the AC slices and sound sequence discrimination learning support the hypothesis that the former is involved in the cellular mechanisms underlying the latter.