Mechanisms of Dendritic Tiling

树突状平铺的机制

基本信息

批准号：
10372981
负责人：
Christopher Tzeng
金额：
$ 3.14万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2022-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10372981
关键词：
Actins Afferent Neurons Anterior Biological Biological Assay Biological Models Caenorhabditis elegans Calcium Calcium Channel Cells Cellular biology Complex Cues Cytoskeleton Dendrites Detection Development Disease Etiology Event Future Genes Genetic Growth Head Human Image Knowledge Label Laboratories Lateral Lead Length Ligands Light Mediating Molecular Morphology Mosaicism Mutation Nature Nematoda Nervous system structure Neural Cell Adhesion Molecule L1 Neurons Pathology Patients Pattern Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Positioning Attribute Postdoctoral Fellow Preventive measure Process Proteins Regulation Reporter Sensory Signal Transduction Skin Stereotyping Stimulus Subcutaneous Tissue Synapses Testing Therapeutic Touch sensation Transgenic Organisms Trees Universities cellular imaging disorder prevention extracellular genetic approach genetic regulatory protein in vivo in vivo evaluation insight mutant nerve supply nervous system disorder neural circuit neuronal cell body novel novel strategies receptive field segregation sensory system transcription factor two-dimensional voltage

项目摘要

Dendrites have diverse morphologies that are important for the neuron to properly process synaptic information. The spatial patterning of a neuron’s dendritic arbor with respect to that of its neighbor is particularly relevant in sensory systems where stimulus detection must be efficient for downstream processing. In a phenomenon called dendritic tiling, neurons from a functional class that encode the same stimuli segregate into distinct mosaic patterns so that their dendrites rarely overlap with one another. Such dendritic tiling allows for spatial acuity by the nonredundant coverage of a receptive field. Specific Aim 1 will test the hypothesis that activity-dependent mechanisms result in tiling of dendrites in the nematode C. elegans using live imaging of neighboring neurons labeled with distinct fluorescent reporters. In Specific Aim 2, genetic approaches will be utilized to assess the impact of extracellular ligands on downstream actin regulation necessary for tiling. This proposal will yield insights into the cell biology of how dendrites from adjacent neurons avoid one another, as well as the novel mechanisms that regulate dynamic growth and retraction of dendrites during neural circuit assembly. Because dendritic pathologies have been observed in human patients with intellectual disorders, the proposed studies will also have applications that can contribute to potential therapies and preventative measures of neurological diseases.

树突具有潜水形态，对于神经元正确处理突触信息很重要。神经元的树突状乔木相对于其邻居的空间图案在感觉系统中特别相关，在这种系统中，刺激检测必须有效地进行下游处理。在一种称为树突瓷砖的现象中，来自功能类别的神经元编码相同的刺激性分类为不同的镶嵌图，因此它们的树突很少彼此重叠。这种树突状瓷砖可以通过接收场的非冗余覆盖范围来实现空间敏锐度。具体目标1将检验以下假设：使用具有不同荧光报告基因的邻近神经元的活成像，秀丽隐杆线虫中的树突偏见。在特定的目标2中，将利用遗传方法评估细胞外配体对平铺所需的下游肌动蛋白调节的影响。该建议将对细胞生物学产生洞察力，即来自相邻神经元的树突如何相互避免，以及在神经元电路组装过程中调节树突的动态生长和缩回的新型机制。由于已经在患有智力障碍的人类患者中观察到了树突状病理，因此拟议的研究还将有可能有助于神经系统疾病的潜在疗法和预防措施。