Mechanisms of Dendritic Tiling

树突具有不同的形态，这对神经元正确处理突触信息非常重要。在感觉系统中，神经元树突状树枝相对于其邻近神经元的空间模式尤其相关，在那里刺激检测必须对下游处理有效。在一种被称为树突平铺的现象中，来自编码相同刺激的功能类别的神经元分离成不同的马赛克图案，因此它们的树突很少相互重叠。这种树枝状瓷砖可以通过非冗余的感受性视野覆盖来实现空间敏锐度。特定目标1将使用标记有不同荧光记者的邻近神经元的实时成像来验证这一假设，即活动依赖机制导致线虫树突的瓦片。在具体目标2中，将利用遗传方法来评估细胞外配体对拼接所需的下游肌动蛋白调控的影响。这一提议将对相邻神经元的树突如何相互回避的细胞生物学产生见解，以及在神经电路组装过程中调节树突动态生长和收缩的新机制。由于已经在人类智力障碍患者中观察到树突病理，拟议的研究也将应用于神经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.