MECHANISMS UNDERLYING MONOCULAR DEPRIVATION

单眼剥夺的潜在机制

• 批准号: 2398085
• 负责人: BARBARA GORDON-LICKEY
• 金额: $ 24.06万
• 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 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2398085
• 关键词: NMDA receptors; binocular vision; brain mapping; developmental neurobiology; digital imaging; immunocytochemistry; in situ hybridization; laboratory rat; messenger RNA; molecular site; neural plasticity; neurotransmitters; polymerase chain reaction; receptor binding; visual cortex; visual deprivation; visual pathways; western blottings

The development of vision in children and other young mammals involves a critical period when synaptic connectivity in the visual cortex can be altered by visual experience. As the brain matures synaptic plasticity diminishes, leaving the visual connections in a more stable state. The loss of plasticity limits the brain's capacity for further adaptation or recovery from injury. The discovery of methods for extending or reinstating synaptic plasticity would have profound therapeutic implications. We and others hypothesize that plasticity is regulated by a type of glutamate receptor called the NMDA receptor. NMDA receptors exist in a number of molecular forms determined by alternative subunit composition and alternative splicing of mRNA. Two recent findings suggest the hypothesis that changes in the composition and resultant physiological properties of NMDA receptors are responsible for developmental changes in plasticity. First, experiments in recombinant systems have shown that physiological responses to glutamate vary with receptor composition. Second, receptor composition changes during cortical development. After testing the relations between receptor composition, physiology and plasticity in visual cortex, we will ask whether these relationships are more than correlative by manipulating the plastic and testing for linked changes in NMDA receptor development. In the first experiments we will examine the development of receptor composition using in situ hybridization and immunohistochemistry. Second we will use whole cell recording, followed by PCR or immunohistochemistry, to ask whether, on a cell by cell basis, the relation between receptor composition and receptor physiology in real neurons is similar to that already known in recombinant systems. Third, having defined correlations between NMDA receptor composition, physiology, and visual plasticity, we will use dark rearing, intraocular tetrodotoxin and drug treatment (MK-801) to perturb the plastic period and/or receptor development. We will then ask whether the changes in development of receptor composition and physiology occur in synchrony with changes in plasticity. Finding that the effects of these perturbation are synchronous will greatly strengthen the hypothesis that synaptic plasticity in the visual cortex is controlled by NMDA receptors.

儿童和其他年轻哺乳动物的视力发展涉及 视觉皮层中突触连通性的关键时期 随着视觉体验的改变。 随着大脑的成熟突触可塑性 减小，使视觉连接处于更稳定的状态。 这 损失可塑性限制了大脑进一步适应的能力或 从伤害中恢复。 发现用于扩展或 恢复突触可塑性将具有深刻的治疗性 含义。 我们和其他人假设可塑性受一种类型的调节 谷氨酸受体称为NMDA受体。 NMDA受体存在于 由替代亚基组成确定的分子形式的数量 和mRNA的替代剪接。 最近的两个发现表明 假说的组成和生理变化 NMDA受体的特性负责发育变化 在可塑性中。 首先，已显示重组系统的实验 对谷氨酸的生理反应因受体组成而变化。 其次，受体组成在皮质发育过程中的变化。 后 测试受体组成，生理和 视觉皮层中的可塑性，我们将询问这些关系是否是 通过操纵塑料和测试链接而不仅仅是相关的 NMDA受体开发的变化。 在第一个实验中，我们将检查受体的发展 使用原位杂交和免疫组织化学的组成。 第二，我们将使用全细胞记录，然后使用PCR或 免疫组织化学，询问在细胞基础上是否在细胞上询问 真实的受体组成与受体生理之间的关系 神经元与重组系统中已经知道的神经元相似。 第三， 在NMDA受体组成之间定义的相关性， 生理学和视觉可塑性，我们将使用黑暗饲养，眼内 四毒素和药物治疗（MK-801）扰动塑料时期 和/或受体开发。 然后，我们将询问是否更改 受体组成和生理的发展发生在同步中 随着可塑性的变化。 发现这些影响 扰动是同步的，将大大加强假设 视觉皮层中的突触可塑性由NMDA控制 受体。