Study for evaluation of dark-rearing effects in mouse visual cortex and for identification of developmental plasticity related molecules

小鼠视觉皮层暗育效应评价及发育可塑性相关分子鉴定研究

基本信息

批准号：
11680814
负责人：
MATAGA Nobuko
金额：
$ 2.3万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Experience-dependent plasticity in the kitten visual cortex is a well-documented phenomenon, however, the molecular and cellular basis for this plasticity remains unknown. Recently we have reported that ocular dominance (OD) plasticity level can be estimated even in the binocular zone of mouse visual cortex. In this study, we first examined whether dark-rearing (DR) delays the functional critical period of OD plasticity in mouse visual cortex as in other species. 1) Adult C57bl/6 mice raised in the total absence of vision retained sensitivity to brief monocular deprivations (MD) at an age when light-reared counterparts (LD) were no longer plastic. 2) Glutamate and GABA contents in DR adult animal were similar to LD. 3) development of parvalbumin positive interneurons was retarded in the binocular zone of DR compared to LD. These results indicate that the critical period is prolonged in older animals by DR. This is the first report about DR experiment using mouse visual cortex.Previous our finding indicates that an activity-dependent immediate early gene (egr1) expression was up-regulated in glutamic acid decarboxylase (GAD65) knockout mice (KO), which impaired OD plasticity. To know whether egr-1 is involved in OD plasticity, we examined MD effect in egr-1 KO. Although egr-1 is thought to be an essential gene for OD plasticity, normal OD shift was found in egr-1 KO mouse visual cortex when their one eye was closed for 4・days during ehe critical period. To identify candidate molecules for the regulation of OD plasticity, we performed the proteome analysis using tPA KO mice, which is second animal model with a disruption in OD plasticity. We found that annexine VI expression pattern was completely different between wt and tPA KO after 4-days MD during the critical period. Further experiments will be necessary to know the relationship between this protein and OD plasticity.

小猫视觉皮层中的经验依赖性可塑性是有据可查的现象，但是，这种可塑性的分子和细胞基础仍然未知。最近，我们报告说，即使在小鼠视觉皮层的双眼区域，也可以估计眼部优势（OD）可塑性水平。在这项研究中，我们首先检查了黑暗抚养（DR）是否像其他物种一样延迟了小鼠视觉皮层的OD可塑性的功能关键时期。 1）在完全缺乏视力的情况下，成年C57BL/6小鼠在灯光射线（LD）不再是塑料的时代，对短暂的单眼剥夺（MD）的敏感性保留了短暂的单眼剥夺（MD）。 2）成人动物中的谷氨酸和GABA含量与LD相似。 3）与LD相比，在DR的双眼区域中，白蛋白阳性中间神经元的发育受阻。这些结果表明，DR延长了较老的动物的关键时期。这是关于使用小鼠视觉皮质的DR实验的第一份报告。我们的发现表明，在谷氨酸脱羧酶（GAD65）基因敲除小鼠（KO）中，活性依赖性的早期基因（EGR1）表达上调，可损害可塑性。要知道EGR-1是否涉及OD可塑性，我们检查了EGR-1 KO中的MD效应。尽管EGR-1被认为是OD可塑性的必不可少的基因，但在关键时期内闭上一只眼睛4天时，在EGR-1 KO小鼠视觉皮层中发现了正常的OD偏移。为了鉴定候选分子以调节OD可塑性，我们使用TPA KO小鼠进行了蛋白质组分析，这是第二种动物模型，其OD可塑性破坏。我们发现，在关键时期4天后，WT和TPA KO之间的附件VI表达模式完全不同。需要进一步的实验才能了解该蛋白质和OD可塑性之间的关系。