2016, Vol. 32
2. 沈阳医学院2015级研究生 ;
3. 沈阳医学院2013级麻醉本科 ;
4. 沈阳医学院2012级临床本科
学习和记忆对生存至关重要，记忆可以使人们预测可能要发生的事情并因此而改变行为。大脑无法容纳生活中的每个细节，亦不能对这些细节产生相等的记忆。记忆是一个基本的认知过程，促进其他所有的重要的认知功能。没有记忆人们就不能思考，大多数动物也能展示出它们对经验的记忆。然而，不能把对所有经验的记忆等量化。一些新经验的记忆之所以能维持恒久，因为它们很容易被大脑处理并与已存在的记忆完好地适应并结合[1]，记忆是通过重复和提取来加强的[2]。本文对脑内杏仁核及情绪激发在参与记忆持久保持中的作用研究进展综述如下。
1 情绪激发与持久记忆激发情绪的经历更容易被记住。一些不愉快的经历：如一场车祸、一次抢劫，会比日常琐事记得更清晰[3]。愉快时刻如生日，假期和婚礼也能很好地被记住。对事件的记忆强度随事件的情感意义而变化。1989年旧金山地震时靠近当地的人们在地震数月后的记忆好于亚特兰大的居民[4]。“9.11事件”发生的3年后，那些袭击时处于曼哈顿市区的人们比那些处在距事发地几英里的人们对袭击有着更深刻的记忆[3]。
记忆是通过给人留下深刻印象的事情所协助，如激情、恐惧、惊讶、羞愧、快乐。记忆巩固的时间依赖过程是通过学习后的条件刺激来调节。研究表明:训练后即刻给小鼠或大鼠实施低强度的中枢神经系统刺激可提高记忆[5]。情绪激发可诱导肾上腺素和皮质醇(大鼠为皮质酮)的释放，记忆巩固过程中，激发情绪的训练经历可使这些激素水平提高。多种训练进行后给予大鼠肾上腺素和皮质酮可增强记忆[6, 7]。此外，肾上腺素受体及糖皮质激素受体拮抗剂可阻断情绪激发及肾上腺应激激素对记忆巩固的效应[8, 9, 10]。很多研究应激激素影响作用的实验已经涉及了与应激训练相关的记忆，例如：应激刺激较小的训练后给予应激激素可提高记忆，包括奖赏记忆[11]。另据报道[12]：多因素慢性应激，可引起动物脑内神经递质、神经激素和下丘脑－垂体－肾上腺轴改变，导致动物行为和学习记忆功能损害。
2 脑内杏仁核参与记忆过程 2.1 杏仁核激活与记忆调节肾上腺应激激素可增强大脑对引起其释放的事件进行记忆。研究表明：肾上腺素对记忆的影响可能是由投射到脑的外周迷走神经激活所引发[13]。学习后对升迷走神经进行直接电刺激可增强记忆[14]。皮质醇可自由进入大脑，并能激活脑内的糖皮质激素受体。
杏仁核可能作为调节应激激素的重要脑区影响记忆的巩固。研究发现:大鼠在训练后对其杏仁核进行短暂的低强度电刺激可增强记忆[15]。早期研究表明：大鼠训练后杏仁核内注射β-肾上腺素受体拮抗剂可损伤记忆巩固，同时注入去甲肾上腺素可阻断该损伤[16]。另据研究报道，全身性给予肾上腺素可导致脑内去甲肾上腺素的释放[17]，引起记忆巩固的肾上腺素升高可被杏仁核内注入心得安阻断[18]。研究认为：在动物训练后杏仁核基底外侧区(basolateral region of amygdala，BLA)去甲肾上腺素的激活可提高大脑对训练经历的记忆能力[19]。大鼠训练后杏仁核内注射β-肾上腺素受体拮抗剂可削弱记忆并阻断全身给予皮质酮及肾上腺素提高记忆的效果[20]。这些发现表明，糖皮质激素诱导的记忆巩固需要杏仁核去甲肾上腺素受体的激活。情绪激发引起的去甲肾上腺素受体的激活似乎使糖皮质激素对记忆巩固的调节成为可能[21]。
很多相关研究表明，情绪激发的训练经历可能增加杏仁核内去甲肾上腺素的释放，足休克训练增加杏仁核内去甲肾上腺素的释放[22]，释放量明显增多的大鼠表现出更好的记忆保持力[23]。此外，一些提高记忆的药物，包括gamma-aminobutyric acid(GABA)能及阿片肽能受体拮抗剂，均可增加杏仁核去甲肾上腺素的释放[24]。
2.2 杏仁核对其他脑区的影响杏仁核与包括皮质在内脑区有着丰富的联系，参与记忆过程的不同方面。杏仁核通过向其他脑区投射神经纤维而影响记忆的巩固[25]。研究表明：海马参与空间学习记忆[26, 27]，尾状核参与反应相关的空间线索学习记忆[28]。Packard等[29]研究发现：水迷宫实验中，杏仁核的训练后活化可增强动物对位置及线索学习的记忆。McIntyre[30]发现，在大鼠，杏仁核基底外侧区去甲肾上腺素受体的激活增强记忆巩固并提高海马内活动调节骨架蛋白(activity-regulated cytoskeletal,Arc)的表达。这些研究表明：Arc参与调节突触可塑性和记忆巩固[31]。
3 情绪激发，肾上腺应激激素和人类记忆研究表明，情绪激发对人类的影响与动物相吻合。学习中或学习后的情绪激活可增强长时程记忆，与肾上腺素及皮质醇有关。然而，影响记忆力的经历不必是强烈的情绪。研究表明,受试者面对带有轻微情绪内容的图片和文字(无论积极还是消极)，其产生记忆增强的效果明显高于没有情绪内容的图片和文字[32]。因此，通过对情绪激发图片的观察可增强记忆能力[33]。
3.1 情绪激发调节记忆巩固研究表明，受试者学习之后进行情绪激发诱导可增强记忆[34]。受试者学习一组单词后立即或延迟一定时间(最长45 min)看一小段能激发情绪的喜剧或悲剧录像，一周后进行评价，结论是学习后30 min内进行录像观看无论悲、喜剧可增强记忆。大学生在讲座后观看激发情绪的视频剪辑，2周后的考试结果明显好于没有看到视频的学生[35]。
大量研究表明，情绪激发对记忆巩固的影响与肾上腺素和皮质醇有关。在受试者观看一组激发情绪的图片前给予肾上腺素受体拮抗剂-心得安，一周后测试表明情绪激发对记忆的增强效果被阻断[36]。给受试者展示激发情绪的图片后立即给予肾上腺素或冷加压应激(通过将一只手放入冰水里诱导，引起肾上腺素和皮质酮的释放)，可提高受试者对图片的记忆力[37, 38]。Hupbach等[39]报导：记忆检索测试后由冷加压应激引发的情绪激发提高唾液皮质醇并在测试的数天后增强对测试内容的记忆。
据报道，肾上腺素受体的激活选择性地影响因情绪激发刺激产生的记忆[40]。在聆听一些中性的和情绪化的单词后进行冷加压应激诱导可在受试后的第2天选择性地提高对情绪化的单词记忆。在冷加压应激后立即测定皮质酮和唾液α-淀粉酶(去甲肾上腺素能系统激活的2种生物标记物)的水平发现其与随后的记忆表现有高度的相关性[41]。另外，Segal等[42]指出：给受试者观察一系列情绪性和中性图片后即刻测定唾液α-淀粉酶水平，在1周记忆保持力测试研究中发现：该水平与受试者对这些情绪性图片的记忆存在明显的选择相关性。在暴露于情绪激发图片后测出的唾液α-淀粉酶水平也与随后从类似图片中成功辨别出见过的图片这一记忆力评价有很强的相关性[43]。这种辨别力有海马的参与[44]。
3.2 情绪激发对记忆的影响包括杏仁核的激活应用PET成像的最初研究中，Cahill[45]由观看情绪激发电影引起的杏仁核激活与3周后测试的对影片的记忆力有高度相关性。随后使用positron emission tomography(PET)成像技术进行研究也有类似报道[46]。使用magnetic resonance image(MRI)成像技术发现了学习过程中杏仁核激活与直接随情绪激活的强度变化而变化的记忆之间的关系，而且激发的情绪是积极还是消极并不是关键[47]。影像学研究提供的证据与动物研究获得的证据一致：情绪激活对长时程记忆巩固的影响涉及到学习过程中杏仁核与其他脑区的相互作用，包括海马[48, 49]。使用功能MRI技术对人脑进行影像学的研究发现：情绪激发对记忆的影响涉及杏仁核去甲肾上腺素能系统的激活。心得安阻断情绪激活刺激引发的杏仁核活化以及随后对该刺激的记忆[50]。给予肾上腺素能药物育亨宾及氢化可的松可增强杏仁核及海马的活化进而改善记忆[51]。
4 小 结综上所述，大部分人的大脑无法容纳生活中的每个细节，亦不能对这些细节产生相等的记忆。选择性地记住更重要的经历似乎是最好的策略，情绪激发时所释放的肾上腺素和皮质酮可调节长时程记忆的巩固，杏仁核可能作为调节应激激素的重要脑区影响记忆的巩固。脑内神经元投射复杂，神经递质种类繁多，它们是通过何种分子机制及通路在各记忆相关脑区及核团之间相互协调完成持久记忆有待进一步研究。
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