Deficit in Selective and Divided Attention Associated with Cholinergic Basal Forebrain Immunotoxic Lesion Produced by 192-Saporin; Motoric/Sensory Deficit Associated with Purkinje Cell Immunotoxic Lesion Produced by OX7-Saporin
Deficit in Selective and Divided Attention Associated with Cholinergic Basal Forebrain Immunotoxic Lesion Produced by 192-Saporin; Motoric/Sensory Deficit Associated with Purkinje Cell Immunotoxic Lesion Produced by OX7-Saporin
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DOI：
10.1006/nlme.1998.3884
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发表时间：
1999-05
影响因子：
2.7
通讯作者：
J. Waite;M. L. Wardlow;A. E. Power
中科院分区：
文献类型：
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作者：
J. Waite;M. L. Wardlow;A. E. Power
免疫毒素192-皂苷注入大鼠侧脑室，破坏前脑基底核团的胆碱能神经元。胆碱能完全丧失所需的剂量也会杀死一些浦肯野细胞。免疫毒素OX7-Saporin在大鼠脑室注射时，以与192-Saporin相似的方式破坏浦肯野细胞，而不影响胆碱能神经元。因此，我们使用OX7-Saporin来区分192-Saporin对小脑损伤和胆碱能细胞丢失的行为影响。选择三种剂量的192-皂苷(1.6、2.6和3.3微克/只大鼠)和一种剂量的OX7-皂苷(2.0微克/只鼠)，产生的浦肯野损失相当于两个最高剂量的192-皂苷。Fischer-344组大鼠在多项选择反应时任务中进行训练，并在损毁后用更复杂的任务重新测试。他们还在水迷宫、被动回避、声音惊吓和开阔场地进行了测试。OX7-Saporin组在许多测试中显示出变化，表明运动亢进和感觉障碍。192-Saporin组与OX7-Saporin组的不同之处在于，在引入新挑战的多项选择反应时任务中，他们表现出缺陷，包括使用噪音干扰物，缩短和延长试验间隔，以及使用9种而不是5种光源。192-皂苷组在其他任务中没有表现出损害。胆碱能基底前脑损毁可以掩盖小脑损伤的部分影响，达到一定的阈值后，脑室注射192-皂苷时，浦肯野细胞丢失的影响占主导地位。
The immunotoxin 192-saporin, infused intracerebroventricularly into rats, destroys cholinergic neurons in the basal forebrain nuclei. Doses required for complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7-saporin, when infused intraventricularly into rats, destroys Purkinje cells in a pattern similar to that produced by 192-saporin, without affecting cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholinergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained in the multiple choice reaction time task and retested with more complex tasks after lesioning. They were also tested in the water maze, passive avoidance, acoustic startle, and open field. The OX7-saporin group exhibited changes in many tests suggesting hypermotility and sensory deficits. The 192-saporin groups differed from the OX7-saporin group when they displayed deficits in multiple choice reaction time tasks in which novel challenges were introduced, including sessions with a noise distractor, shortened and lengthened intertrial intervals, and use of nine instead of five sources of light stimulus. The 192-saporin groups showed no impairment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which effects of Purkinje cell loss predominate when 192-saporin is administered intraventricularly.