Mechanisms of Dendritic Tiling

树突具有不同的形态，对于神经元正确处理突触信息是重要的。神经元的树突乔木相对于其邻居的空间图案化在感觉系统中特别相关，其中刺激检测必须对下游处理有效。在一种称为树突平铺的现象中，来自一个功能类别的神经元编码相同的刺激，分离成不同的马赛克模式，因此它们的树突很少相互重叠。这种树突状平铺允许通过感受野的非冗余覆盖来获得空间敏锐度。具体目标1将测试的假设，活性依赖的机制，导致平铺的树突在线虫C。elegans使用不同的荧光报告标记的邻近神经元的实时成像。在具体目标2中，遗传方法将被用来评估细胞外配体对平铺所需的下游肌动蛋白调节的影响。这个建议将产生深入了解细胞生物学的树突如何从相邻的神经元避免彼此，以及新的机制，调节动态生长和神经回路组装过程中的树突的收缩。由于在患有智力障碍的人类患者中观察到了树突状病变，因此拟议的研究也将有助于神经系统疾病的潜在治疗和预防措施。

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.