MECHANISMS OF VISUAL PLASTICITY

哺乳动物的视觉系统需要经验才能正常发育。 由于一个人的视觉输入退化而缺乏感官体验 眼睛在发育过程中可能导致不可逆转的视觉功能丧失 由这只眼睛调停。这种情况被称为弱视，是一种主要的 儿童视力残疾的原因。毫无疑问，关于 这种类型的神经具有重要的科学和临床意义 可塑性。然而，潜在的细胞和分子机制 这一关键的发展过程仍然未知。近几年来， 人们的注意力集中在N-甲基-D-天冬氨酸(NMDA)亚型上 兴奋性氨基酸受体，因为它在大脑中被认为是作用的 发展、学习和记忆。它在视觉上的特殊作用 然而，可塑性仍然难以捉摸。最新分子 研究提供了一个令人兴奋的新机会来研究 NMDA受体对视觉功能和可塑性的贡献。 这些研究表明，这种受体是由不同的 亚基蛋白质和不同亚基组合展示 独特的功能特性。这里提出的是发展 NMDA受体亚单位组成的变化起着至关重要的作用 在视觉可塑性方面。提出了一种新的方法来检验这一点。 假设。皮质内注射反义DNA将被用于 抑制选定的NMDA受体亚单位。然后受体应该是 由剩余的亚基组装而成。中的结果修改 大脑皮层NMDA受体的功能特性将通过 体外存活的大脑皮层脑片的细胞内记录 而视觉反应的变化将在正常动物身上进行评估 以及那些被单眼剥夺视力的人 反义治疗。这种方法提供了几个重要的 相对于目前使用的药理学程序的优势，例如 有选择地操纵单个亚基的可能性。此外， 转基因动物不能用来进行这些实验，因为 缺乏某些NMDA受体亚单位的动物是不能存活的。结果是 应该描绘出NMDA的分子组成之间的联系 受体及其在视皮层中的功能作用。此外，由于 分子干预有一天可能被用于治疗 视力障碍，这些研究可能为我们的 在突触水平上的临床医疗设备。

The mammalian visual system requires experience to develop normally. Lack of sensory experience due to degradation of the visual input of one eye during development may lead to irreversible loss of visual function mediated by this eye. This condition, known as amblyopia, is a major cause of visual disability in children. There is no doubt regarding the substantial scientific and clinical relevance of this type of neural plasticity. However, the cellular and molecular mechanisms underlying this crucial developmental process remain unknown. In recent years much attention has been focused on the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor because of its proposed role in brain development, learning and memory. Its specific role in visual plasticity has, nevertheless, remained elusive. Recent molecular studies have provided an exciting new opportunity to examine the contribution of the NMDA receptor to visual function and plasticity. These studies have shown that this receptor is composed of different subunit proteins and that different combinations of subunits exhibit distinct functional properties. It is proposed here that developmental changes in subunit composition of the NMDA receptor play a critical role in visual plasticity. A novel approach is proposed to examine this hypothesis. Intracortical infusion of antisense DNA will be used to suppress selected NMDA receptor subunits. The receptors should then be assembled from the remaining subunits. The resultant modifications in functional properties of cortical NMDA receptors will be examined by intracellular recordings in cortical slices maintained living in vitro and the changes in visual responses will be assessed in normal animals as well as in those which were monocularly deprived of vision during antisense treatment. This approach offers several significant advantages over currently used pharmacological procedures, such as the possibility of selectively manipulating individual subunits. Moreover, transgenic animals cannot be used to conduct these experiments, since animals lacking some NMDA receptor subunits are not viable. The results should delineate links between the molecular composition of the NMDA receptor and its functional role in visual cortex. In addition, since molecular interventions may one day be used for therapeutic purposes in visual disorders, these studies may provide a new dimension to our clinical armamentarium at the level of the synapse.