Cacucci Francesca, Yi Ming, Wills Thomas J, Chapman Paul, O'Keefe John
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7863-8. doi: 10.1073/pnas.0802908105. Epub 2008 May 27.
Alzheimer's disease (AD) is associated with progressive memory decline. Hippocampal place cells are a well understood candidate for the neural basis of one type of memory in rodents; these cells identify the animal's location in an environment and are crucial for spatial memory and navigation. We have recorded place cells in the Tg2576 mouse model of AD, and we report that aged (16 mo) but not young (3 mo) transgenic mice show degraded neuronal representations of the environment. The level of place cell degradation correlates with the animals' (poorer) spatial memory as tested in a forced-choice spatial alternation T-maze task and with hippocampal, but not neocortical, amyloid plaque burden. Place cell recording provides a sensitive assay for measuring the amount and rate of functional deterioration in animal models of dementia as well as providing a quantifiable physiological indication of the beneficial effects of potential therapies.
阿尔茨海默病（AD）与进行性记忆衰退相关。海马位置细胞是啮齿动物一种记忆类型的神经基础中被充分了解的候选者；这些细胞识别动物在环境中的位置，对空间记忆和导航至关重要。我们在AD的Tg2576小鼠模型中记录了位置细胞，并且我们报告称，老年（16个月）而非年轻（3个月）的转基因小鼠表现出环境的神经元表征退化。位置细胞退化的程度与在强制选择空间交替T迷宫任务中测试的动物（较差的）空间记忆相关，并且与海马而非新皮质的淀粉样斑块负荷相关。位置细胞记录为测量痴呆动物模型中功能衰退的量和速率提供了一种灵敏的检测方法，同时也为潜在疗法有益效果提供了可量化的生理指标。
