Sound sequence discrimination learning dependent on cholinergic input to the auditory cortex

在大鼠听觉皮层（AC）切片中，异突触刺激后的突触增强受诱导刺激序列的影响。据推测，这种序列依赖的可塑性可能部分参与了声音序列区分的细胞机制。毒蕈碱受体拮抗剂可消除序列依赖性。因此，我们研究了声音序列识别学习对大鼠AC胆碱能输入的依赖性。缺水的老鼠被训练去区分两种声音成分的序列，而对两种可能序列中的一种做出舔舐行为的老鼠则被奖励水。试验随机呈现奖励序列（S+）或未奖励序列（S-），每1分钟重复一次，共4天，共12小时。S+和S-分别计算大鼠舔舐喷口的试验百分比，并以差值估计测试性能。毒蕈碱受体拮抗剂阿托品（10 mg/kg, i.p）对声音序列辨别学习的影响更大，而毒蕈碱受体拮抗剂甲基拉托品（10 mg/kg, i.p）不能穿过血脑屏障，对毒蕈碱受体无显著影响。在4天的测试过程中，声音序列识别水平的提高维持了一周以上。阿托品对获得性生产性能无影响。将胆碱能免疫毒素192igg -皂苷注射到双侧交流弱音序列识别学习中，两种声音成分的识别不受影响。利诺匹定是一种抑制m型K^+电流的认知增强剂，在阿托品存在的情况下，恢复AC切片突触增强的序列依赖性。在本研究中，利诺匹定也恢复了被192igg -皂苷削弱的声音序列识别学习。AC切片中序列依赖的可塑性和声音序列辨别学习之间的这些相似性支持了前者参与后者背后的细胞机制的假设。少

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 … More 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