NF186 in GABAergic domain specific synaptic targeting

GABA 能域特异性突触靶向中的 NF186

• 批准号: 7055497
• 负责人: HONG YANG
• 金额: $ 5.04万
• 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/7055497
• 关键词: GABA receptor; axon; biological signal transduction; cell adhesion molecules; confocal scanning microscopy; cytoskeleton; developmental neurobiology; gamma aminobutyrate; gene expression; genetically modified animals; immunocytochemistry; innervation; laboratory mouse; neocortex; nerve growth factors; neural information processing; neural transmission; postdoctoral investigator; protein localization; protein structure function; pyramidal cells; soma; synapses

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（从神经元兴奋性到同步性）发挥着重要作用。不同类别的 GABA 能突触被分为亚细胞域（即树突、胞体、轴突初始段-AIS），从而差异性地调节主要神经元的输入、整合和输出。 GABA 能突触的亚细胞靶向机制仍然很大程度上未知。我们实验室最近的工作证明了 L1 家族免疫球蛋白细胞粘附分子 (IgCAM)、神经成束蛋白 186 (NF186) 及其基于锚蛋白的膜骨架在 GABA 能突触靶向小脑浦肯野神经元 AIS 中的重要作用。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 能神经支配引导至主要神经元（例如新皮质中的锥体神经元）的体细胞/AIS。我们将通过检查 GABA 能突触靶向过程中 NF186 的空间和时间表达，并通过遗传、生化和成像方法的组合来操纵 NF186 的分布和功能来检验这一假设。