MECHANISMS UNDERLYING THE MONOCULAR DEPRIVATION EFFECT

单眼剥夺效应的机制

• 批准号: 3258522
• 负责人: BARBARA GORDON-LICKEY
• 金额: $ 23.72万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3258522
• 关键词: NMDA receptors; acetylcholine; autoradiography; binocular vision; brain mapping; calcium channel blockers; cats; cell morphology; cerebral dominance; developmental neurobiology; dizocilpine; experimental brain lesion; infant animal; lateral geniculate body; molecular site; neural plasticity; norepinephrine; receptor binding; visual cortex; visual deprivation; visual pathways

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（研究者的摘要）：这项研究的长期目标 是要了解成熟过程中可塑性的降低 哺乳动物神经系统。 调查人员使用视觉系统研究 这个问题有两个原因。 首先，视觉系统更改 当动物被剥夺了正常的视觉环境时，急剧。 这些变化可用于评估可塑性。 第二，缺陷 人类婴儿的视觉系统会导致永久视觉缺陷，除非 缺陷很早纠正。 最终，调查人员希望 找到在人类视觉系统中保持可塑性的方法 允许以后纠正视觉缺陷和其他类型的损害 由于环境逆境。 该提议着重于 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，结合为 NMDA受体的标记。 飞行员工作证明了MK-801 受体在最大期间的密度最高 因此，可塑性，因此可能在确定何时视觉 系统是塑料。 第一组实验探索了 NMDA受体功能与视觉下降之间的关系 可塑性。 在这些实验中，调查人员问：（1）是否是 MK-801结合位点的开发和下降与发展相似 视觉皮层可塑性的下降； （2）MK-801中的变化是否 结合位点特异性是视觉皮层。 （3）是否改变 结合位点特异于MK-801结合位点； （4）是否 结合位点的层流位置随着年龄的增长而变化； （5）是否 绑定尺寸的属性随时间课程的变化而变化 可塑性的时间课程。 以上所有问题将解决 具有匀浆结合和受体结合自显影术。 这 下一组实验询问NMDA通道的封锁是否改变 视觉皮层可塑性。 这些实验涉及缝合一只眼睛 大约12天，询问缝合线的影响是否通过 用MK-801处理。 缝合线的效果将通过记录来测定 来自视觉皮层。 最后一组实验与可塑性有关 去甲肾上腺素（NE）和乙酰胆碱（ACH）产生的变化 MK-801治疗导致的可塑性变化的耗竭。 以前的 工作表明NE和ACH对于维护也很重要 可塑性。 该组的第一个实验询问NMDA是否 刺激NE和ACH释放随着年龄的变化而变化，无论此释放是否为 通过体内MK-801治疗修饰，以及是否有任何修改是年龄的 依赖。 第二个实验询问NE和ACH的耗尽是否耗尽 改变NMDA受体的数量和分布。