Selective cholinergic depletion of the hippocampus spares both behaviorally induced arc transcription and spatial learning and memory
Selective cholinergic depletion of the hippocampus spares both behaviorally induced arc transcription and spatial learning and memory
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DOI：
10.1002/hipo.20261
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发表时间：
2007-01-01
期刊：
影响因子：
3.5
通讯作者：
Rapp, Peter R.
中科院分区：
文献类型：
--
作者：
Fletcher, Bonnie R.;Baxter, Mark G.;Rapp, Peter R.
我们先前证明，当海马依赖的学习和可塑性受到穹窿病变的损害时，行为诱导的直接早期基因Arc的表达相应较低。内侧隔和垂直斜带是皮层下传入神经的主要来源，这些传入神经通过穹窿支配海马。在这里，我们评估了来自这些区域的胆碱能传入对穹窿病变产生的空间学习障碍和Arc转录行为诱导的具体贡献。使用免疫毒素192 igg皂苷，在内侧隔和垂直对角带产生选择性胆碱能细胞体病变。然后在桡臂水迷宫中对大鼠进行提示和空间延迟匹配任务的训练。192个igg -皂苷损伤的动物在水迷宫中可以正常学习线索和地点识别任务，而在从线索切换到空间任务时，只显示出轻微和短暂的损伤。在行为测试之后，大鼠依次探索了两种已知可诱导海马锥体神经元Arc表达的新环境。与完全穹窿横断的影响形成鲜明对比的是，定量原位放射自显像显示假手术动物和病变动物CA1、CA3或辐射层中Arc mRNA的表达没有差异。从这些数据得出的结论是，单独的胆碱能神经传导障碍不能解释穹窿病变引起的空间学习缺陷或Arc转录行为诱导受损。(c) 2007 Wiley-Liss, Inc。
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. (c) 2007 Wiley-Liss, Inc.