Miyashita Y, Kameyama M, Hasegawa I, Fukushima T
Department of Physiology, The University of Tokyo School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113, Japan.
Neurobiol Learn Mem. 1998 Jul-Sep;70(1-2):197-211. doi: 10.1006/nlme.1998.3848.
Neuropsychological theories have proposed a critical role for the interaction between the medial temporal lobe and the neocortex in the formation of long-term memory for facts and events, which has often been tested by learning of a series of paired words or figures in humans. We have examined neural mechanisms underlying the memory "consolidation" process by single-unit recording and molecular biological methods in an animal model of a visual pair-association task in monkeys. In our previous studies, we found that long-term associative representations of visual objects are acquired through learning in the neural network of the anterior inferior temporal (IT) cortex. In this article, we propose the hypothesis that limbic neurons undergo rapid modification of synaptic connectivity and provide backward signals that guide the reorganization of neocortical neural circuits. Two experiments tested this hypothesis: (1) we examined the role of the backward connections from the medial temporal lobe to the IT cortex by injecting ibotenic acid into the entorhinal and perirhinal cortices, which provided massive backward projections ipsilaterally to the IT cortex. We found that the limbic lesion disrupted the associative code of the IT neurons between the paired associates, without impairing the visual response to each stimulus. (2) We then tested the first half of this hypothesis by detecting the expression of immediate-early genes in the monkey temporal cortex. We found specific expression of zif268 during the learning of a new set of paired associates in the pair-association task, most intensively in area 36 of the perirhinal cortex. All these results with the visual pair-association task support our hypothesis and demonstrate that the consolidation process, which was first proposed on the basis of clinico-psychological evidence, can now be examined in primates using neurophysiolocical and molecular biological approaches.
神经心理学理论认为，内侧颞叶与新皮质之间的相互作用在事实和事件的长期记忆形成中起着关键作用，这一点常通过人类学习一系列配对单词或图形来进行测试。我们通过单单元记录和分子生物学方法，在猴子视觉配对联想任务的动物模型中研究了记忆“巩固”过程的神经机制。在我们之前的研究中，我们发现视觉对象的长期联想表征是通过前颞下（IT）皮质神经网络中的学习获得的。在本文中，我们提出一个假说，即边缘系统神经元的突触连接会迅速改变，并提供反向信号来引导新皮质神经回路的重组。两项实验对这一假说进行了验证：（１）我们通过向内嗅皮质和嗅周皮质注射鹅膏蕈氨酸，来研究从内侧颞叶到IT皮质的反向连接的作用，这会向IT皮质同侧提供大量反向投射。我们发现，边缘系统损伤破坏了配对联想物之间IT神经元的联想编码，但并未损害对每个刺激的视觉反应。（２）然后，我们通过检测猴子颞叶皮质中即早基因的表达，对这一假说前半部分进行了验证。我们发现在配对联想任务中学习一组新的配对联想物时，zif268有特异性表达，在嗅周皮质36区最为强烈。所有这些关于视觉配对联想任务的结果都支持了我们的假说，并表明最初基于临床心理学证据提出的巩固过程，现在可以在灵长类动物中使用神经生理学和分子生物学方法进行研究。
