A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning.
A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning.
复制标题
经典眨眼条件反射中隔海马活动的胆碱能破坏的计算模型。
DOI：
10.1006/nlme.1996.0043
复制
发表时间：
1996
影响因子：
2.7
通讯作者：
Gluck,MA
中科院分区：
文献类型：
--
作者：
Myers,CE;Ermita,BR;Harris,K;Hasselmo,M;Solomon,P;Gluck,MA
先前的皮质-海马区相互作用的神经计算模型(Gluck&Myers，1993)可以为检验经典条件反射过程中隔-海马区调节的行为效应提供一个框架。该模型假设，在学习过程中，海马区是形成新的刺激表征所必需的，但不是形成简单联系所必需的。本文考虑隔-海马区的相互作用如何影响这一功能。隔核为海马体提供了几种调制输入，包括一种胆碱能输入，Hasselmo(1995)认为它可能在两种状态之间的连续体上调节海马体的动力学：一种是存储状态，在这种状态下，传入的信息被编码为中期记忆；另一种是当该信息被重新激活时的回忆状态。根据这一理论，像东莨菪碱这样的抗胆碱能药物应该会选择性地降低海马体存储新信息的能力，从而扰乱学习。在大脑皮层-海马区模型中，可以通过对海马体学习速率的简单操作来实现对哈塞尔莫想法的近似；这种操作在形式上等同于调整海马体在学习和回忆状态中花费的时间。通过这种操作，该模型成功地解释了东莨菪碱在延缓人(所罗门，Groccia-Ellison，Flynn，Mirak，Edwards，Dunehew，&Stanton，1993)和动物(所罗门，Soloman，van der Schaaf，&Perry，1983)经典条件反射中的作用。该模型进一步预测，尽管胆碱能激动剂(如他克林)可能会改善人为压低脑乙酰胆碱水平的受试者的学习能力，但这种胆碱能疗法对正常受试者记忆的改善可能是有限的。这与正常受试者胆碱能药物的U型剂量反应曲线的普遍发现是一致的：低到中等剂量可以改善学习，但更高的剂量是无效的，甚至降低学习(例如，Ennaceur&Meliani，1992；Dumery，Derer，&Blozovski，1988；等)。
A previous neurocomputational model of corticohippocampal interaction (Gluck & Myers, 1993) can provide a framework for examining the behavioral effects of septohippocampal modulation during classical conditioning. The model assumes that the hippocampal region is necessary for forming new stimulus representations during learning, but not for the formation of simple associations. This paper considers how septohippocampal interaction could affect this function. The septal nuclei provide several modulatory inputs to the hippocampus, including a cholinergic input which Hasselmo (1995) has suggested may function to regulate hippocampal dynamics on a continuum between two states: a storage state in which incoming information is encoded as an intermediate-term memory and a recall state when this information is reactivated. In this theory, anticholinergic drugs such as scopolamine should disrupt learning by selectively reducing the hippocampus's ability to store new information. An approximation of Hasselmo's idea can be implemented in the corticohippocampal model by a simple manipulation of hippocampal learning rate; this manipulation is formally equivalent to adjusting the amount of time the hippocampus spends in learning and recall states. With this manipulation, the model successfully accounts for the effects of scopolamine in retarding classical conditioning in hu- mans (Solomon, Groccia-Ellison, Flynn, Mirak, Edwards, Dunehew, & Stanton, 1993) and animals (Solomon, Soloman, van der Schaaf, & Perry, 1983). The model further predicts that although cholinergic agonists (such as Tacrine) may improve learning in subjects with artificially depressed brain acetylcholine levels, there may be limited memory improvement in normal subjects from such cholinergic therapy. This is consistent with the general finding of a U-shaped dose response curve for cholinergic drugs in normal subjects: low to moderate doses may improve learning, but higher doses are ineffective or even degrade learning (e.g., Ennaceur & Meliani, 1992; Dumery, Derer, & Blozovski, 1988; etc.).