NF186 in GABAergic domain specific synaptic targeting

GABA 能域特异性突触靶向中的 NF186

• 批准号: 7214852
• 负责人: HONG YANG
• 金额: $ 5.2万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214852
• 关键词: Axon; Biochemical Genetics; Biological Neural Networks; Brain; Cell Adhesion Molecules; Cerebellum; Chromosome Pairing; Class; Dendrites; Family; Image; Immunoglobulins; Interneurons; Laboratories; Membrane; Neocortex; Neural Cell Adhesion Molecule L1; Neurons; Output; Physiological; Play; Property; Pyramidal Cells; Range; Role; Signal Transduction; Skeleton; Synapses; Testing; Work; base; hippocampal pyramidal neuron; nerve supply; neurofascin; neuronal cell body; neuronal excitability

DESCRIPTION (provided by applicant): GABAergic inhibition plays important roles in many aspects of neural network properties ranging from neuronal excitability to synchrony. Distinct classes of GABAergic synapses are segregated into subcellular domains (i.e. dendrite, soma, axon initial segment-AIS), thereby differentially regulating the input, integration and output of principal neurons. The mechanisms underlying the subcellular targeting of GABAergic synapses remain largely unknown. Recent work in our laboratory has demonstrated an essential role for an L1 family immunoglobulin cell adhesion molecule (IgCAM), neurofascin186 (NF186) and its underlying ankyrinG-based membrane skeleton in the targeting of GABAergic synapses to AIS of Purkinje neurons in cerebellum. Here we hypothesize that the subcellular localization and signaling of NF186 is a general mechanism which directs GABAergic innervation to soma/AIS of principal neurons, such as pyramidal neurons in neocortex. We will test this hypothesis by examining the spatial and temporal expression of NF186 during GABAergic synapse targeting, and by manipulating the distribution and function of NF186 through a combination of genetic, biochemical and imaging approaches.

描述（由申请人提供）：GABA能抑制在神经网络特性的许多方面起着重要作用，从神经元兴奋性到同步。不同类别的GABA能突触被隔离为亚细胞结构域（即树突，soma，轴突初始部分AIS），从而差异地调节主神经元的输入，积分和输出。 GABA能突触的亚细胞靶向基础的机制在很大程度上未知。我们实验室的最新工作表明，L1家族免疫球蛋白细胞粘附分子（IGCAM），Neurofascin186（NF186）及其基于脚踝的基于脚踝的膜骨架在Gabaergic Synapes of purkinje ofkinje ofkinje ofkinje neuroons in Cerebellym中。在这里，我们假设NF186的亚细胞定位和信号传导是一种通用机制，它将GABA能神经定向到主要神经元的SOMA/AIS，例如Neocortex中的锥体神经元。我们将通过检查GABA能突触靶向期间NF186的空间和时间表达，以及通过遗传，生化和成像方法的结合来测试NF186的空间和时间表达。