Bunce Jamie G, Sabolek Helen R, Chrobak James J
Department of Psychology, University of Connecticut, Storrs, Connecticut 06269, USA.
Hippocampus. 2004;14(4):450-9. doi: 10.1002/hipo.10200.
The medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. A large number of studies have demonstrated that direct intraseptal drug infusions can produce amnestic or promnestic effects. While a few studies have examined the effects of direct intraseptal infusion of cholinomimetics on spatial memory performance (with drug "on-board" at the time of testing), the effects of post-acquisition infusions have not been assessed. We hypothesized that post-acquisition intraseptal infusion of cholinomimetics, by promoting hippocampal theta and suppressing the occurrence of hippocampal sharp waves, may disrupt the long-term retention and consolidation of memory. The present study examined the effects of intraseptal infusion of the cholinergic agonist carbachol in a delayed-non-match-to-sample radial maze task. Treatments were administered immediately following (within 1 min) the sample session with a retention session 2 h later. Carbachol infusions (12.5-125 ng in 0.5 microl) produced a linear dose-dependent decrease in correct entries and increase in retroactive errors, without any change in proactive errors or latency-per-choice. These findings suggest that post-acquisition intraseptal cholinergic treatments can produce amnesia. These findings are discussed with regard to multi-stage models of hippocampal-dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age-related cognitive decline and Alzheimer's dementia.
内侧隔核调节海马结构的生理功能和新兴功能（如记忆形成）。该核中胆碱能受体特别丰富，是拟胆碱能认知增强药物开发的假定靶点。大量研究表明，直接向隔区内注射药物可产生遗忘或促进记忆的作用。虽然有一些研究考察了直接向隔区内注射拟胆碱药物对空间记忆表现的影响（在测试时药物“在体内”），但获取后注射的影响尚未评估。我们假设，获取后向隔区内注射拟胆碱药物，通过促进海马θ波并抑制海马尖波的出现，可能会扰乱记忆的长期保持和巩固。本研究在延迟非匹配样本放射状迷宫任务中考察了向隔区内注射胆碱能激动剂卡巴胆碱的影响。在样本训练后立即（1分钟内）给药，并在2小时后进行保持训练。注射卡巴胆碱（0.5微升中含12.5 - 125纳克）导致正确进入次数呈线性剂量依赖性减少，逆向错误增加，而前摄错误或每次选择的潜伏期没有任何变化。这些发现表明，获取后向隔区内进行胆碱能处理可导致遗忘。结合海马依赖性记忆形成的多阶段模型以及治疗轻度认知障碍、年龄相关认知衰退和阿尔茨海默病痴呆的治疗策略的进一步发展对这些发现进行了讨论。
