Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys
Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys
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DOI：
10.1093/cercor/12.7.729
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发表时间：
2002-07-01
期刊：
影响因子：
3.7
通讯作者：
Gaffan, D
中科院分区：
文献类型：
--
作者：
Easton, A;Ridley, RM;Gaffan, D
有人提出，将颞叶下部皮质和内侧叶与其胆碱能传入分离会导致严重的顺行性遗忘症。为了直接验证这一假设，七只恒河猴接受了基底前脑胆碱能细胞的单侧免疫毒性损伤，并对穹隆进行了损毁。在第二次手术中，对侧的颞叶下部皮质被消融。所有动物在学习视觉场景和物体-奖赏联系方面都受到严重损害。学习场景中的损伤与基底前脑胆碱能细胞的丢失有关，而与全身组织损伤无关。两只猴子作为手术对照组，注射生理盐水代替免疫毒素，但所有其他程序都相同，并且没有像那些有免疫毒素损伤的猴子那样严重受损。以往的工作表明，双侧前颞叶干部(颞叶白质)、杏仁核和穹隆的猴子表现出严重的新的学习障碍，并提供了一个人类内侧颞叶健忘症的模型。这种联合消融的一个效果是将下颞叶皮质和内侧颞叶从其胆碱能传入中分离出来，可能还会直接破坏海马体系统。因此，本研究的结果提供了内侧颞叶健忘症和阿尔茨海默病之间的新的联系，在阿尔茨海默病中，胆碱能基底前脑表现为病理。我们认为，在这两种情况下，记忆障碍都是由于将下颞叶皮质和内侧颞叶从其胆碱能传入中分离出来，可能还包括对海马体系统的直接破坏。
It has been proposed that isolation of the inferior temporal cortex and medial temporal lobe from their cholinergic afferents results in a severe anterograde amnesia. To test this hypothesis directly, seven rhesus monkeys received a unilateral immunotoxic lesion of the cholinergic cells of the basal forebrain with an ipsilesional section of the fornix. In a second surgery, inferior temporal cortex was ablated in the opposite hemisphere. All animals were severely impaired at learning visual scenes and object-reward associations. The impairment in learning scenes was correlated with cholinergic cell loss in the basal forebrain, but not with generalized tissue damage. Two monkeys served as surgical controls with saline injection in place of the immunotoxin, but all other procedures the same, and were not as severely impaired as those with immunotoxic lesions. Previous work has shown that monkeys with bilateral section of the anterior temporal stem (white matter of the temporal lobe), amygdala and fornix show a severe new learning impairment, and provide a model of human medial temporal lobe amnesia. One effect of this combined ablation is to isolate inferior temporal cortex and medial temporal lobe from their cholinergic afferents, possibly in addition to a direct disruption of the hippocampal system. The results of the present study, then, provide a novel link between the mechanisms of medial temporal lobe amnesia and Alzheimer's disease in which the cholinergic basal forebrain shows pathology. We propose that in both cases the mnemonic impairments result from isolating inferior temporal cortex and medial temporal lobe from their cholinergic afferents, possibly in addition to a direct disruption of the hippocampal system.