Quantitiative model for the development of neural topographic maps

描述（由申请人提供）：我们的目标是了解大脑中神经网络在发育过程中形成的定量原理。 从视网膜到视顶盖或哺乳动物上级丘的局部投影是研究这些原理的理想候选者。 邻近视网膜细胞的轴突终止于近端的上级丘，从而形成视觉世界的地形精确表示，称为地形图或视网膜拓扑图。 坐标轴通过分子标记的分级表达在视网膜和靶标中编码，所述分子标记例如Eph受体酪氨酸激酶及其配体肝配蛋白。 相关的神经活动促进了投射的进一步锐化。 在这个建议中，我们将联合收割机各种发展机制在一个单一的定量模型，并显示它们的相互作用如何提供所需的精度的地形图。 （一）如何在同一模式中将联合收割机依赖活动的因素和不依赖活动的因素结合起来？ 2.为什么轴突和树突在发育过程中的动力学不同？ （3）突触成熟在轴突和树突分支动力学中的作用是什么？ 我们的项目将有助于理解遗传程序的分子标记形式和相关神经活动传达的环境信息塑造发育中的神经元连接的机制。 因此，我们的研究将提供以感觉功能异常发育为特征的神经系统疾病的见解，包括Eph/ ephrin通路中断对人类视觉处理损伤的可能影响。 我们的模型将有助于解决与电路缺陷相关的发育障碍和神经退行性疾病。 所有研究都将与实验小组密切合作进行。 将在项目的所有阶段征求专家意见。

DESCRIPTION (provided by applicant): Our goal is to understand the quantitative principles whereby neural networks in the brain are formed during development. An ideal candidate to study these principles is the topographic projection from retina to optic tectum or mammalian superior colliculus. Axons of neighboring retinal cells terminate proximally in the superior colliculus thus forming a topographically precise representation of the visual world called topographic or retinotopic map. Coordinate axes are encoded in retina and in the target through graded expression of molecular labels, such as Eph receptor tyrosine kinases and their ligands, ephrins. Additional sharpening of projections is facilitated by correlated neural activity. In this proposal we will combine various developmental mechanisms in a single quantitative model and show how their interactions provide required precision of topographic mapping. The specific aims of this proposal include: i) How can one combine activity-dependent and activity-independent factors in the same model? ii) Why is the dynamics of axons and dendrites different during development? iii) What is the role of synaptic maturation in the axon and dendrite branch dynamics? Our project will help to understand the mechanisms whereby genetic program in the form of molecular labels and environmental information conveyed by correlated neural activity shape the developing neuronal connectivity. Our study will therefore provide insights on neurological conditions characterized by abnormal development of sensory function, including a possible effect of disruption of Eph/ ephrin pathways on impairment of visual processing in humans. Our model will aid in addressing developmental disabilities and neuro-degenerative diseases linked to defects in circuitry. All studies will be carried out in close collaboration with experimental groups. Expert advice will be solicited on all stages of the project.