Miyashita Y, Morita M, Naya Y, Yoshida M, Tomita H
Department of Physiology, University of Tokyo School of Medicine, Japan.
C R Acad Sci III. 1998 Feb-Mar;321(2-3):185-92. doi: 10.1016/s0764-4469(97)89820-4.
Neuropsychological theories proposed a critical role of the interaction between the medial temporal lobe and 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 identify neural mechanisms of this long-term memory formation process by single-unit recording and molecular biological methods in an animal model of visual pair-association task in monkeys. In our previous studies, we found a group of neurons that manifested selective responses to both of the paired associates (pair-coding neuron) in the anterior inferior temporal (IT) cortex. It provides strong evidence that single IT neurons acquire the response-selectivity through associative learning, and suggests that the reorganized neural circuits for the pair-coding neurons serve as the memory engram of the pair-association learning. In this article, we investigated further mechanisms of the neural circuit reorganization. First, we tested the role of the backward connections from the medial temporal lobe to IT cortex. Ibotenic acid was injected unilaterally into the entorhinal and perirhinal cortex which provided massive backward projections ipsilaterally to 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. Second, we ask why the limbic-neocortical interactions are so important. We hypothesize that limbic neurons would undergo rapid modification of synaptic connectivity and provide backward signals that guide reorganization of neocortical neural circuits. We then investigated the molecular basis of such rapid synaptic modifiability by detecting the expression of immediate-early genes. We found strong expression of zif268 during the learning of a new set of paired associates, most intensively in area 36 of the perirhinal cortex. All these results with 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 the primate with neurophysiolocical and molecular biological approaches.
神经心理学理论提出，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关键作用，这一作用常通过人类学习一系列配对单词或图形来进行测试。我们在猴子视觉配对联想任务的动物模型中，通过单神经元记录和分子生物学方法，确定了这种长期记忆形成过程的神经机制。在我们之前的研究中，我们发现了一组在前颞下（IT）皮质中对两个配对联想物均表现出选择性反应的神经元（配对编码神经元）。这提供了强有力的证据，表明单个IT神经元通过联想学习获得反应选择性，并表明配对编码神经元的重组神经回路充当配对联想学习的记忆印迹。在本文中，我们进一步研究了神经回路重组的机制。首先，我们测试了从内侧颞叶到IT皮质的反向连接的作用。将异博定单侧注射到内嗅皮质和嗅周皮质，这些区域向同侧IT皮质提供大量反向投射。我们发现，边缘系统损伤破坏了IT神经元在配对联想物之间的联想编码，但不影响对每个刺激的视觉反应。其次，我们探究了边缘系统与新皮质相互作用为何如此重要。我们假设边缘系统神经元的突触连接性会迅速改变，并提供反向信号来指导新皮质神经回路的重组。然后，我们通过检测即刻早期基因的表达，研究了这种快速突触可塑性的分子基础。我们发现在学习一组新的配对联想物时，zif268有强烈表达，在嗅周皮质的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设，并表明最初基于临床心理学证据提出的“巩固”过程，现在可以用神经生理学和分子生物学方法在灵长类动物中进行研究。
