McMahan R W, Sobel T J, Baxter M G
Department of Psychology, University of North Carolina at Chapel Hill, USA.
Hippocampus. 1997;7(2):130-6. doi: 10.1002/(SICI)1098-1063(1997)7:2<130::AID-HIPO2>3.0.CO;2-R.
The septo-hippocampal cholinergic pathway has traditionally been thought of as essential for spatial memory. Recent studies have demonstrated intact spatial learning following removal of this pathway with an immunotoxin selective for cholinergic neurons. In the present experiment, rats with selective removal of hippocampal cholinergic input were tested in a delayed nonmatching-to-position task in a water version of the radial arm maze. This allowed us to increase and parametrically vary the memory load compared with the standard Morris water maze (by varying the delay between the initial four choices and the final four choices) to determine if this would reveal a deficit in rats with lesions of septo-hippocampal cholinergic projections. Male Long-Evans rats were given injections of 192 IgG-saporin, a selective immunotoxin for cholinergic neurons, into the medial septum/vertical limb of the diagonal band (MS/VDB) to remove cholinergic projections to the hippocampus, or a control surgery. The rats were trained on the radial maze task following surgery. An escape platform was located at the end of each arm of the maze and was removed after an arm was utilized for escape. After initial training, a delay was interposed between the first four trials and the second four trials. Errors during the second four-trial component were scored in two categories: retroactive (reentering an arm chosen before the delay) and proactive (reentering an arm chosen after the delay). Retroactive errors increased as delay increased (from 60 s to 6 h) but were equivalent in control and MS/VDB-lesion groups. Proactive errors did not vary with delay and were also unaffected by the lesion. Radioenzymatic assays for choline acetyltransferase activity in the hippocampus of lesioned rats confirmed a significant loss of cholinergic input from the MS/VDB. These results indicate that normal spatial working memory is possible after substantial loss of septo-hippocampal cholinergic projections.
传统上认为，隔区 - 海马胆碱能通路对空间记忆至关重要。最近的研究表明，用对胆碱能神经元具有选择性的免疫毒素去除该通路后，空间学习能力依然完整。在本实验中，选择性去除海马胆碱能输入的大鼠在放射状臂迷宫水迷宫版的延迟位置非匹配任务中接受测试。与标准的莫里斯水迷宫相比，这使我们能够增加并参数化地改变记忆负荷（通过改变最初四个选择和最后四个选择之间的延迟），以确定这是否会揭示隔区 - 海马胆碱能投射受损大鼠的缺陷。给雄性Long - Evans大鼠在内侧隔区/斜角带垂直支（MS/VDB）注射192 IgG - 皂草素（一种对胆碱能神经元具有选择性的免疫毒素），以去除通向海马的胆碱能投射，或进行对照手术。术后对大鼠进行放射状迷宫任务训练。逃生平台位于迷宫各臂的末端，在某臂用于逃生后将其移除。初始训练后，在最初四次试验和后四次试验之间插入延迟。后四次试验部分的错误分为两类：追溯性（重新进入延迟前选择的臂）和前瞻性（重新进入延迟后选择的臂）。追溯性错误随着延迟增加（从60秒到6小时）而增加，但在对照组和MS/VDB损伤组中相当。前瞻性错误不随延迟变化，也不受损伤影响。对损伤大鼠海马中胆碱乙酰转移酶活性的放射酶测定证实，来自MS/VDB的胆碱能输入显著丧失。这些结果表明，在隔区 - 海马胆碱能投射大量丧失后，正常的空间工作记忆仍有可能。
