| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In rat auditory cortex (AC) slices, synaptic potentiation following heterosynaptic stimulation is affected by 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. Water-deprived 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. Either rewarded (S+) or unrewarded (S-) sequence was presented randomly in a trial, which was repeated every one minute for 12 hours in 4 days. Percentage of trials in which rats licked the spout was calculated separately for S+ and S-, and test performance was estimated as the difference. Atropine (10 mg/kg, i.p.), an antagonist
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of muscarinic receptors, attenuated sound sequence discrimination learning, while methylatropine (10 mg/kg, i.p.), a muscarinic receptor antagonist unable to cross the blood-brain barrier, had no significant effect. Increased level of sound sequence discrimination during 4 days test session was maintained more than one week. Atropine had no effect on the acquired performance. Injection of the cholinergic immunotoxin 192IgG-saporin into the bilateral AC attenuated sound sequence discrimination learning, while discrimination between the two sound components was not affected. Linopirdine, a cognitive enhancer that inhibit M-type K^+ currents, restores the sequence dependence of synaptic potentiation in AC slices in the presence of 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. Less
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