Nelson A, Sowinski P, Hodges H
Department of Psychology, Institute of Psychiatry, London, United Kingdom.
Neurobiol Learn Mem. 1997 May;67(3):228-47. doi: 10.1006/nlme.1996.3758.
In order to assess effects of global ischemia in tasks of spatial learning and working memory, male Wistar rats were subjected to four vessel occlusion (4 VO) for periods of 5, 10, and 20 min and compared with sham-operated controls over four test phases, from 6 to 54 weeks after surgery. Rats were assessed on acquisition in the water maze, a task that is sensitive to ischemic impairments, before testing in Skinner box and water maze working memory tasks, which both require the short-term storage of information, but make different demands on spatial information processing. Phases 1 and 3 assessed spatial learning in a standard water maze procedure (12 and 10 training days, 2 trials/day with a 10-min intertrial interval: ITI). Phase 2 involved training and testing in delayed non-matching-to-position task in the Skinner box, with delays of 2-10 s between the information and choice stages. Phase 4 examined working memory in a water maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a novel platform position on each day. Ischemic rats showed duration-related impairments in water maze acquisition and working memory, but not in the less spatially demanding Skinner box task. Since water maze acquisition deficits were seen both before and after testing in the Skinner box the lack of effect cannot be attributed to time or to prior training. Ischemic deficits were more marked in Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be progressive. Histological assessment showed that cell loss was largely confined to the hippocampal CA1 field and was linearly related to duration of occlusion. At the maximal level of loss (5.7 mm before the interaural line) the 20-min group showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not differ from controls, less than 10% loss. Only the 20-min group showed significant damage beyond the CA1 field, ranging from 30-40% loss in the CA3 field to 5% loss in one striatal area. No cortical damage was seen. The extent of CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and working memory scores, but not with trials to criterion in the Skinner box task. There were significant correlations between different measures both within and between water maze tasks, but not Skinner box tasks, suggesting that the two types of procedure engaged different cognitive processes. The results indicate that the intrahippocampal damage induced by 4 VO impaired tasks which required processing of allocentric spatial information, but did not impair the storage of limited spatial information in working memory.
为了评估全脑缺血对空间学习和工作记忆任务的影响，将雄性Wistar大鼠进行四血管闭塞（4VO）处理5、10和20分钟，并在术后6至54周的四个测试阶段与假手术对照组进行比较。在斯金纳箱和水迷宫工作记忆任务测试之前，先在对缺血损伤敏感的水迷宫中评估大鼠的习得能力，这两个任务都需要短期存储信息，但对空间信息处理的要求不同。第1阶段和第3阶段在标准水迷宫程序中评估空间学习能力（12天和10天训练，每天2次试验且试验间隔为10分钟）。第2阶段涉及在斯金纳箱中进行延迟位置不匹配任务的训练和测试，信息阶段和选择阶段之间的延迟为2至10秒。第4阶段在水迷宫延迟位置匹配任务中检查工作记忆，每天进行4次试验，试验间隔为30秒，且每天更换新的平台位置。缺血大鼠在水迷宫习得和工作记忆方面表现出与持续时间相关的损伤，但在对空间要求较低的斯金纳箱任务中未出现损伤。由于在斯金纳箱测试之前和之后都观察到水迷宫习得缺陷，因此缺乏影响不能归因于时间或先前的训练。缺血缺陷在习得的第3阶段比第1阶段更明显，表明损伤可能是进行性的。组织学评估显示，细胞损失主要局限于海马CA1区，并且与闭塞持续时间呈线性相关。在最大损失水平（耳间线前5.7毫米处），20分钟组显示90%的损失，10分钟组显示60%的损失，而与对照组无差异的5分钟组损失小于10%。只有20分钟组在CA1区以外显示出明显损伤，CA3区损失范围为30%至40%，一个纹状体区域损失为5%。未观察到皮质损伤。CA1区细胞损失程度与水迷宫习得（第3阶段）和工作记忆分数适度相关，但与斯金纳箱任务达到标准所需的试验次数无关。水迷宫任务内部和之间的不同测量之间存在显著相关性，但斯金纳箱任务不存在，这表明这两种程序涉及不同的认知过程。结果表明，4VO诱导的海马内损伤损害了需要处理以自我为中心的空间信息的任务，但未损害工作记忆中有限空间信息的存储。
