Fletcher Bonnie R, Baxter Mark G, Guzowski John F, Shapiro Matthew L, Rapp Peter R
Fishberg Department of Neuroscience & Alfred B. and Gudrun J. Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA.
Hippocampus. 2007;17(3):227-34. doi: 10.1002/hipo.20261.
We demonstrated previously that when hippocampal-dependent learning and plasticity are compromised by fornix lesions, behaviorally induced expression of the immediate early gene, Arc, is correspondingly low. The medial septum and the vertical diagonal band are major sources of subcortical afferents that innervate the hippocampus via the fornix. Here we assessed the specific contribution of cholinergic afferents from these regions to the impairments in spatial learning and behavioral induction of Arc transcription produced by fornix lesions. The immunotoxin, 192 IgG-saporin, was used to produce selective lesions of cholinergic cell bodies in the medial septum and vertical diagonal band. Rats were then trained on both cued and spatial delayed match-to-place tasks in a radial arm water maze. Animals with 192 IgG-saporin lesions learned both cue and place discrimination tasks in the water maze normally, and showed only a mild and transient impairment when switching from the cued to the spatial version of the task. Following behavioral testing, rats explored two novel environments sequentially in a setting known to induce Arc expression in hippocampal pyramidal neurons. In marked contrast to the effects of complete fornix transection, quantitative in situ autoradiography revealed no differences in Arc mRNA expression between sham and lesion animals in CA1, CA3 or stratum radiatum. The conclusion from these data is that cholinergic deafferentation alone cannot account for the spatial learning deficits or impaired behavioral induction of Arc transcription produced by fornix lesions.
我们之前证实，当穹窿损伤损害海马依赖性学习和可塑性时，行为诱导的即刻早期基因Arc的表达相应降低。内侧隔区和垂直对角带是通过穹窿支配海马的皮质下传入纤维的主要来源。在此，我们评估了来自这些区域的胆碱能传入纤维对穹窿损伤所致空间学习障碍和Arc转录的行为诱导受损的具体作用。免疫毒素192 IgG-皂草素被用于选择性损伤内侧隔区和垂直对角带的胆碱能细胞体。然后，大鼠在放射状臂水迷宫中接受线索性和空间延迟位置匹配任务训练。接受192 IgG-皂草素损伤的动物在水迷宫中正常学习线索性和位置辨别任务，并且在从线索性任务转换为空间任务时仅表现出轻微且短暂的损伤。行为测试后，大鼠在一个已知可诱导海马锥体细胞中Arc表达的环境中依次探索两个新环境。与完全穹窿横断的影响形成鲜明对比的是，定量原位放射自显影显示，在CA1、CA3或辐射层中，假手术组和损伤组动物的Arc mRNA表达没有差异。这些数据得出的结论是，单独的胆碱能传入纤维脱失不能解释穹窿损伤所致的空间学习缺陷或Arc转录的行为诱导受损。
