TOPOGRAPHIC MAPPING LABELS IN VISUAL DEVELOPMENT

描述（由申请人提供）：在视觉系统中，眼睛接收来自外界的刺激并将信息传递到大脑的多个区域，大部分视觉处理发生在这些区域。眼睛中的神经元以精确定义的空间顺序与它们的目标发生突触。这个顺序被认为是正确运作的关键，并且有两个组织特征。每只眼睛与大脑的连接都是按地形排列的，这意味着眼睛神经元的最近邻关系在它们的连接中得到了保留。此外，来自两只眼睛的视觉输入在大脑中以眼睛特定层的形式排列。这一提议的目的是进一步加深我们对精确神经连接的产生的理解。我们正在采用遗传方法，结合经典的轴突追踪技术，剖析遗传决定因素在有序视觉地图生成中的作用。我们主要致力于确定Eph家族受体酪氨酸激酶及其配体ephrin在初级视觉图谱形成中的功能需求。最近的研究表明，ephrin突变小鼠在视网膜轴突向上丘和外侧膝状核的映射上存在缺陷。这些缺陷的性质导致了一种假设，即ephrin对地形测绘和眼睛特异性层的形成都很重要。我们拟通过表征ephrin突变小鼠的视觉投影，并将其与发育中的视觉系统中ephrin表达模式的映射缺陷联系起来，来验证这一点。精确的神经元连接的形成是神经元之间有效交流的严格要求。了解指定视觉系统中适当连接的基本过程将与涉及异常神经元连接和处理的神经系统疾病直接相关，例如全局性癫痫、睡眠障碍和智力低下。这些研究将有助于我们理解视觉信息从一个大脑区域转移到另一个大脑区域的机制。这些机制很可能与损伤或疾病损伤后轴突连接再生所需的机制相同。

DESCRIPTION (provided by applicant): In the visual system, the eye receives stimuli from the outside world and transfers information to multiple areas in the brain, where the bulk of visual processing occurs. Neurons in the eye synapse with their targets with precisely defined spatial order. This order is thought to be crucial for correct functioning, and has two organizing features. Each eye's connections to the brain are arranged topographically, meaning that the nearest neighbor relationships of eye neurons are pre-served in their connections. In addition, visual input from both eyes are aligned in the brain in the form of eye-specific layers. The purpose of this proposal is to further our understanding of the generation of precise neural connectivity. We are taking a genetic approach, combined with classical axonal tracing techniques, to dissect the role of genetic determinants in the generation of ordered visual maps. We are primarily focusing our effort on determining the functional requirements of the Eph family of receptor tyrosine kinases and their ligands, ephrins, in primary visual map formation. Recent work has shown that ephrin-mutant mice have defects in the mapping of retinal axons to both the superior colliculus and the lateral geniculate nucleus. The nature of these defects lead to the hypothesis that ephrins are important for both topographic mapping and eye-specific layer formation. We propose to test this by characterizing the visual projections in ephrin-mutant mice and correlating the mapping defects in with ephrin expression patterns in the developing visual system. The formation of precise neuronal connections is strictly required for productive communication between neurons. Understanding the basic processes that specify proper connectivity in the visual system will be directly relevant to neurological disorders involving aberrant neuronal connections and processing, such as, generalized seizures, sleep disorders and mental retardation. These studies are expected to contribute to our understanding of the mechanism by which visual information is transferred from one brain region to another. The mechanisms are most likely shared with those required for the regeneration of axonal connections after damage due to injury or disease.