Wozniak D F, Stewart G R, Finger S, Olney J W
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110.
Neuroscience. 1989;32(3):685-700. doi: 10.1016/0306-4522(89)90290-x.
Cholinergic neurons in the nucleus basalis region of the forebrain project to various portions of the cerebral cortex, including somatosensory cortex. Degeneration of these neurons and their cortical projections is a major feature of the neuropathology of Alzheimer's disease. Injecting an excitotoxin into the basal forebrain to destroy nucleus basalis neurons provides a potentially useful animal model for studying the role of these neurons in Alzheimer's disease. Previously, we demonstrated that rats with nucleus basalis excitotoxin lesions performed poorly on a tactile discrimination task and on a test of working memory. In an effort to clarify further the role of impaired memory versus other types of impairment (e.g. disrupted somatosensory processing due to cholinergic deafferentation of somatosensory cortex), we compared a group of rats with bilateral nucleus basalis excitotoxin lesions and a group with bilateral somatosensory cortical ablations on a variety of behavioral tasks. Rats with nucleus basalis lesions performed as well as controls on a battery of neurological tests but exhibited increased emotionality unlike rats with somatosensory cortical ablations which performed poorly on the battery but were not hyperemotional. The two lesion groups were impaired significantly and to a comparable degree in performing two-choice tactile discriminations in a T-maze. In contrast, only rats with nucleus basalis lesions showed deficits in working memory as tested in an eight-arm radial maze. Both lesion groups performed comparably to sham controls on a test of reference memory involving a black/white discrimination in a T-maze. The findings suggest that rats with nucleus basalis lesions manifest disturbances in several of the same spheres (emotionality, somatosensory information processing, memory) that are disrupted in Alzheimer's disease and further confirm the utility of the excitotoxin lesion approach for studying the pathophysiology of Alzheimer's disease.
前脑基底核区域的胆碱能神经元投射至大脑皮层的各个部分，包括体感皮层。这些神经元及其皮层投射的退化是阿尔茨海默病神经病理学的一个主要特征。向前脑基底核注射兴奋性毒素以破坏基底核神经元，为研究这些神经元在阿尔茨海默病中的作用提供了一个潜在有用的动物模型。此前，我们证明，患有基底核兴奋性毒素损伤的大鼠在触觉辨别任务和工作记忆测试中表现不佳。为了进一步阐明记忆受损与其他类型损伤（例如由于体感皮层胆碱能传入缺失导致的体感加工中断）的作用，我们在一系列行为任务中比较了一组双侧基底核兴奋性毒素损伤的大鼠和一组双侧体感皮层切除的大鼠。患有基底核损伤的大鼠在一系列神经测试中的表现与对照组一样，但表现出情绪增强，这与体感皮层切除的大鼠不同，后者在这些测试中表现不佳，但没有情绪过度。在T型迷宫中进行二选一触觉辨别时，两个损伤组均显著受损且程度相当。相比之下，在八臂放射状迷宫测试中，只有患有基底核损伤的大鼠表现出工作记忆缺陷。在涉及T型迷宫黑白辨别的参考记忆测试中，两个损伤组的表现与假手术对照组相当。这些发现表明，患有基底核损伤的大鼠在阿尔茨海默病中受到干扰的几个相同领域（情绪、体感信息处理、记忆）中表现出紊乱，并进一步证实了兴奋性毒素损伤方法在研究阿尔茨海默病病理生理学方面的实用性。
