权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

猫视皮层的经验依赖性可塑性是一个有充分证据的现象，然而，这种可塑性的分子和细胞基础仍然不清楚。最近我们报道，即使在小鼠视皮层的双眼区域，也可以估计眼优势(OD)的可塑性水平。在这项研究中，我们首先研究了暗饲养(DR)是否像其他物种一样推迟了小鼠视皮层外径可塑性的功能临界期。1)在完全失明状态下饲养的成年C57BL/6小鼠，在光养小鼠(LD)不再可塑的年龄，仍对短暂的单眼剥夺(MD)保持敏感。2)成年DR动物体内谷氨酸和GABA含量与LD相似。3)与LD相比，DR双眼区小白蛋白阳性中间神经元发育迟缓。这些结果表明，DR延长了老年动物的临界期。这是第一个关于利用小鼠视觉皮质进行DR实验的报道。此前我们的发现表明，谷氨酸脱羧酶(GAD65)基因敲除小鼠(KO)活性依赖的即刻早期基因(Egr1)表达上调，从而削弱了OD的可塑性。为了了解EGR-1是否参与外径可塑性，我们检测了EGR-1 KO的MD效应。虽然EGR-1被认为是OD可塑性的必需基因，但在EHE关键期，EGR-1 KO小鼠视皮层闭眼4d后，其视皮层的OD漂移正常。为了确定OD可塑性调节的候选分子，我们对tPA KO小鼠进行了蛋白质组分析，这是第二个OD可塑性中断的动物模型。我们发现，在关键时期，mD后4d，wt和tPA KO的Annexine VI表达模式完全不同。要了解该蛋白与外径可塑性之间的关系，还需要进一步的实验。