Paban V, Jaffard M, Chambon C, Malafosse M, Alescio-Lautier B
Université d'Aix-Marseille I, Laboratoire de Neurobiologie Intégrative et Adaptative, UMR/CNRS 6149, Avenue Normandie Escadrille Niemen, 13397 Marseille, Cedex 20, France.
Neuroscience. 2005;132(1):13-32. doi: 10.1016/j.neuroscience.2004.11.024.
The present experiment was designed to study changes in behavior following immunolesioning of the basal forebrain cholinergic system. Rats were lesioned at 3 months of age by injection of the 192 IgG-saporin immunotoxin into the medial septum area and the nucleus basalis magnocellularis, and then tested at different times after surgery (from days 7-500) on a range of behavioral tests, administered in the following order: a nonmatching-to-position task in a T-maze, an object-recognition task, an object-location task, and an open-field activity test. The results revealed a two-way interaction between post-lesion behavioral testing time and memory demands. In the nonmatching-to-position task, memory deficits appeared quite rapidly after surgery, i.e. at a post-lesion time as short as 1 month. In the object-recognition test, memory impairments appeared only when rats were tested at late post-lesion times (starting at 15 months), whereas in the object-location task deficits were apparent at early post-lesion times (starting from 2 months). Taking the post-operative time into account, one can hypothesize that at the shortest post-lesion times, behavioral deficits are due to pure cholinergic depletion, while as the post-lesion time increases, one can speculate the occurrence of a non-cholinergic system decompensation process and/or a gradual degeneration process affecting other neuronal systems that may contribute to mnemonic impairments. Interestingly, when middle-aged rats were housed in an enriched environment, 192 IgG-saporin-lesioned rats performed better than standard-lesioned rats on both the nonmatching-to-position and the object-recognition tests. Environment enrichment had significant beneficial effects in 192 IgG-saporin-lesioned rats, suggesting that lesioned rats at late post-lesion times (over 1 year) still have appreciable cognitive plasticity.
本实验旨在研究基底前脑胆碱能系统免疫损伤后行为的变化。在3月龄大鼠的内侧隔区和大细胞基底核注射192 IgG-皂草素免疫毒素进行损伤，然后在术后不同时间（7 - 500天）进行一系列行为测试，测试顺序如下：T迷宫中的位置辨别非匹配任务、物体识别任务、物体定位任务和旷场活动测试。结果显示，损伤后行为测试时间与记忆需求之间存在双向交互作用。在位置辨别非匹配任务中，术后记忆缺陷出现得相当快，即在损伤后短短1个月时就出现了。在物体识别测试中，只有在损伤后较晚时间（从15个月开始）对大鼠进行测试时才出现记忆损伤，而在物体定位任务中，损伤后早期（从2个月开始）就出现了缺陷。考虑到术后时间，可以推测在损伤后最短时间内，行为缺陷是由于单纯的胆碱能耗竭，而随着损伤后时间的增加，可以推测发生了非胆碱能系统失代偿过程和/或影响其他可能导致记忆损伤的神经元系统的逐渐退化过程。有趣的是，当将中年大鼠饲养在丰富环境中时，192 IgG-皂草素损伤的大鼠在位置辨别非匹配任务和物体识别测试中的表现均优于标准损伤的大鼠。环境丰富对192 IgG-皂草素损伤的大鼠有显著的有益影响，这表明损伤后较晚时间（超过1年）的损伤大鼠仍具有相当可观的认知可塑性。
