Simple nervous system approach to the mechanisms of associative learning

联想学习机制的简单神经系统方法

基本信息

批准号：
10480176
负责人：
KIRINO Yutaka
金额：
$ 8.19万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

This work was aimed at clarifying the mechanisms of leaning and memory using physiological and molecular biological methods. First, physiological recordings were made in the procerebrum, which is the olfactory center of the slug, in isolated bran preparations after odor-taste associative conditioning Optical recording of the membrane potential revealed that a cluster of neurons in the procerebrum depolarizes selectively in response to leaned odors.By the mRNA differential display method, we found a gene whose expression elevated specifically after odor-taste associative conditioning, and its sequence has been determined. This gene encoded 121 amino acids, and named LAPS18. To clarify its function, the expression pattern of this gene was determined. The expression of the LAPS18 protein was significantly increased 12-48 h after conditioning compared to the control group. This suggests that the LAPS18 protein is related to the late phase events of learning. Immunohistochemical analysis indicated that LAPS18 protein was present in the entire procerebrum, and localized to the neuropil layers of the procerebrum after conditioning, indicating a conditioning-specific changes in localization. By corUoca1 laser scanning microscopy, the LAPS18 protein was found to be localized to the nerve terminals, especially regions of cell contact. These results suggest that the LAPS18 protein is an extrace11ular matrix protein secreted at nerve terminals and modulate the synaptic connections. The homologue genes of LAPS18 were found in various Vertebrate species. Therefore, LAPS18 was thought to play essential roles in learning and memory.

这项工作旨在利用生理学和分子生物学方法阐明学习和记忆的机制。首先，在经过气味-味觉关联调节后，在分离的麸皮制剂中，在原大脑（蛞蝓的嗅觉中心）中进行了生理记录。膜电位的光学记录表明，原大脑中的一组神经元选择性地去极化，以响应倾斜的气味。通过mRNA差异显示方法，我们发现了一个在气味-味道关联条件作用后表达特异性升高的基因，并且其序列已确定。该基因编码121个氨基酸，命名为LAPS18。为了阐明其功能，确定了该基因的表达模式。与对照组相比，调理后12-48小时LAPS18蛋白的表达显着增加。这表明 LAPS18 蛋白与学习的后期事件有关。免疫组织化学分析表明，LAPS18蛋白存在于整个大脑中，并且在条件反射后定位于大脑的神经纤维层，表明定位特异性的变化。通过 corUoca1 激光扫描显微镜，发现 LAPS18 蛋白定位于神经末梢，尤其是细胞接触区域。这些结果表明 LAPS18 蛋白是神经末梢分泌的一种胞外基质蛋白，可调节突触连接。 LAPS18的同源基因在多种脊椎动物中被发现。因此，LAPS18被认为在学习和记忆中发挥着重要作用。