MECHANISMS UNDERLYING THE MONOCULAR DEPRIVATION EFFECT

单眼剥夺效应的机制

基本信息

批准号：
3258523
负责人：
BARBARA GORDON-LICKEY
金额：
$ 23.91万
依托单位：
UNIVERSITY OF OREGON
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-07-01 至 1996-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (Investigator's Abstract): The long term goal of this research is to understand the decrease in plasticity during maturation of the mammalian nervous system. The investigators use the visual system to study this problem for two reasons. First, the visual system changes dramatically when an animal is deprived of a normal visual environment. These changes can be used to assess plasticity. Second, defects in the visual system of human infants cause permanent visual deficits unless these defects are corrected very early. Eventually, the investigators hope to find methods of maintaining plasticity in the human visual system that will permit later correction of visual deficits and other types of impairment due to environmental adversity. This proposal focuses on the role of N-methyl-d-Aspartate (NMDA) receptors in visual system plasticity. These receptors have been implicated in other types of plasticity. The investigators will use MK-801, a noncompetitive NMDA antagonist, binding as a marker for NMDA receptors. Pilot work has demonstrated that MK-801 receptors have their highest density during the period of maximum plasticity, and therefore, may have a role in determining when the visual system is plastic. The first group of experiments explores the relationship between NMDA receptor function and the decline of visual plasticity. In these experiments the investigators ask: (1) whether the development and decline of MK-801 binding sites parallels the development and decline of visual cortex plasticity; (2) whether the changes in MK-801 binding sites are specific to the visual cortex; (3) whether changes in binding sites are specific to the MK-801 binding site; (4) whether the laminar location of the binding sites changes with age; and (5) whether the properties of the binding size change with a time course similar to the time course of plasticity. All of the above questions will be approached with homogenate binding and with receptor binding autoradiography. The next group of experiments asks whether blockade of NMDA channels alters visual cortex plasticity. These experiments involve suturing one eye for about 12 days, and asking whether the effects of suture are modified by treatment with MK-801. The effects of suture will be assayed by recording from the visual cortex. The final group of experiments relates plasticity changes resulting from norepinephrine (NE) and acetylcholine (ACh) depletion to plasticity changes resulting from MK-801 treatment. Previous work has indicated that NE and ACh are also important for the maintenance of plasticity. The first experiments in this group ask whether NMDA stimulated NE and ACh release changes with age, whether this release is modified by in vivo MK-801 treatment, and whether any modification is age dependent. The second experiments ask whether depletion of NE and ACh alters the number and distribution of NMDA receptors.

描述（研究者摘要）：本研究的长期目标是为了了解在成熟过程中可塑性的下降哺乳动物的神经系统。研究人员使用视觉系统来研究这个问题有两个原因。一、视觉系统的变化当动物被剥夺了正常的视觉环境时，情况会急剧恶化。这些变化可用于评估可塑性。二、缺陷人类婴儿的视觉系统会导致永久性视力缺陷，除非这些缺陷很早就得到纠正。最终，调查人员希望寻找维持人类视觉系统可塑性的方法允许以后矫正视力缺陷和其他类型的障碍由于环境恶劣。该提案的重点是视觉系统可塑性中的 N-甲基-d-天冬氨酸 (NMDA) 受体。这些受体与其他类型的可塑性有关。这研究人员将使用 MK-801，一种非竞争性 NMDA 拮抗剂，结合作为 NMDA 受体的标记。试点工作表明 MK-801 受体在最大时期具有最高密度可塑性，因此可能在决定视觉何时系统是塑料的。第一组实验探索 NMDA受体功能与视力下降的关系可塑性。在这些实验中，研究人员询问：（1）是否 MK-801 结合位点的发展和衰退与发展平行视觉皮层可塑性下降； (2) MK-801是否有变化结合位点是视觉皮层特有的； (3) 是否发生变化结合位点是 MK-801 结合位点特有的； (4) 是否结合位点的层状位置随年龄而变化； (5) 是否结合尺寸的属性随着时间的推移而变化，类似于可塑性的时间过程。上述所有问题都将得到解决匀浆结合和受体结合放射自显影。这下一组实验询问 NMDA 通道的封锁是否会改变视觉皮层的可塑性。这些实验涉及缝合一只眼睛 12天左右，询问缝合效果是否有修改用MK-801治疗。缝合的效果将通过记录进行分析来自视觉皮层。最后一组实验涉及可塑性去甲肾上腺素 (NE) 和乙酰胆碱 (ACh) 引起的变化 MK-801 处理导致的可塑性变化的消耗。以前的工作表明 NE 和 ACh 对于维持也很重要的可塑性。该组的第一个实验询问 NMDA 是否刺激的 NE 和 ACh 释放随年龄而变化，这种释放是否体内MK-801治疗改变，以及是否有任何改变是年龄依赖。第二个实验询问 NE 和 ACh 是否耗尽改变 NMDA 受体的数量和分布。