Quantitiative model for the development of neural topographic maps

神经地形图开发的定量模型

• 批准号: 7761660
• 负责人: ALEXEI KOULAKOV
• 金额: $ 41.58万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7761660
• 关键词: Address; Axon; Biological Neural Networks; Brain; Cells; Collaborations; Data; Defect; Degenerative Disorder; Dendrites; Development; Developmental Disabilities; Eph Family Receptors; Ephrins; Genetic Programming; Goals; Human; Imagery; Impairment; Internet; Label; Ligands; Link; Maps; Modeling; Molecular; Mutant Strains Mice; N-Methyl-D-Aspartate Receptors; Nature; Neurologic; Neurons; Operative Surgical Procedures; Pathway interactions; Procedures; Publications; Resources; Retina; Retinal; Role; Rotation; Sensory; Shapes; Software Tools; Staging; Synapses; Tectum Mesencephali; Testing; Time; Vertebrates; Vesicle; Visual; base; design; genetic manipulation; insight; model development; relating to nervous system; retinotectal; retinotopic; simulation; software development; superior colliculus Corpora quadrigemina; visual process; visual processing

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.

描述（由申请人提供）：我们的目标是了解大脑神经网络在发育过程中形成的定量原理。 研究这些原理的理想候选者是从视网膜到视顶盖或哺乳动物上丘的地形投影。 邻近视网膜细胞的轴突近端终止于上丘，从而形成视觉世界的地形精确表示，称为地形图或视网膜专题图。 坐标轴通过分子标记（例如 Eph 受体酪氨酸激酶及其配体、肝配蛋白）的分级表达在视网膜和目标中进行编码。 相关的神经活动有助于预测的进一步锐化。 在本提案中，我们将在一个定量模型中结合各种发育机制，并展示它们的相互作用如何提供地形测绘所需的精度。 该提案的具体目标包括：i）如何在同一模型中结合活动依赖和活动无关因素？ ii) 为什么轴突和树突的动力学在发育过程中不同？ iii) 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分子标签形式的遗传程序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，我们的研究将为以感觉功能异常发育为特征的神经系统疾病提供见解，包括 Eph/ephrin 通路破坏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。 将在项目的各个阶段征求专家意见。