van der Staay F Josef, Bouger Pascale, Lehmann Olivia, Lazarus Christine, Cosquer Brigitte, Koenig Julie, Stump Veronika, Cassel Jean-Christophe
CNS Research, Bayer, Wuppertal, Germany.
Hippocampus. 2006;16(12):1061-79. doi: 10.1002/hipo.20229.
In rats, nonspecific mechanical or neurotoxic lesions of the septum impair spatial memory in, e.g., Morris water- and radial-maze tasks. Unfortunately, the lack of specificity of such lesions limits inferences about the role of the cholinergic hippocampal projections in spatial cognition. We therefore tested the effects of septal lesions produced by 192 IgG-saporin in rats, which is highly selective for basal forebrain cholinergic neurons, on home cage activity, noncognitive tests (modified Irwin test, open field and forced swimming tests, and various sensorimotor tasks), and the cone-field spatial learning task. The immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (-61%) and hippocampus (>-75%). Rats with lesions showed mild home-cage hyperactivity at 4 weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the cone-field task, rats with septal lesions made more working- and reference-memory errors than the controls, but acquisition curves were parallel in both groups. The speed of visiting cones was faster in the rats with lesions, indicative of disturbed attention or increased motivation. These data support the growing evidence that involvement of the septohippocampal cholinergic system in spatial learning and memory may have been overestimated in studies that used lesions with poor selectivity.
在大鼠中，例如在莫里斯水迷宫和放射状迷宫任务中，中隔的非特异性机械性或神经毒性损伤会损害空间记忆。不幸的是，此类损伤缺乏特异性，限制了关于胆碱能海马投射在空间认知中作用的推断。因此，我们测试了192IgG-皂草素对大鼠造成的中隔损伤的影响，192IgG-皂草素对基底前脑胆碱能神经元具有高度选择性，该损伤对笼内活动、非认知测试（改良欧文测试、旷场和强迫游泳测试以及各种感觉运动任务）以及锥场空间学习任务的影响。免疫毒性损伤降低了中隔（-61%）和海马（>-75%）中的乙酰胆碱（ACh）水平。有损伤的大鼠在损伤后4周表现出轻度的笼内活动亢进，但在手术后13周没有非认知缺陷。在锥场任务中，有中隔损伤的大鼠比对照组出现更多的工作记忆和参考记忆错误，但两组的习得曲线是平行的。有损伤的大鼠访问锥体的速度更快，表明注意力受到干扰或动机增加。这些数据支持了越来越多的证据，即在使用选择性较差的损伤的研究中，海马胆碱能系统在空间学习和记忆中的参与程度可能被高估了。
