Dynamics of cerebellar Purkinje cell dendrites

这项建议的长期目标是了解调节细胞内蛋白质的分子和细胞机制。 小脑神经元回路的发展。树突棘，许多突起上的突触输入位点 诸如小脑浦肯野细胞的神经元是高度动态的结构， 发展规律。在发育过程中调节脊柱动力学的机制不是 知道的在这里，我们将使用多光子活体成像的神经元结构在器官型切片和在体内， 结合电子显微镜来研究突触维持的机制。我们的中央 有一种假说认为，胶质细胞的鞘化过程对树突棘的运动和突触的形成起着关键性的调节作用。 稳定在第一个目标中，我们将描述伯格曼神经胶质过程的发展， 动力学成像方法。在第二个目标中，我们将测试神经胶质细胞如何调节脊柱动力学。 通过测量神经胶质增强减少的遗传模型中的脊柱运动性来增强神经胶质增强。第三个目标 我们将确定EphA受体和ephrin配体在神经胶质-脊髓串扰和调节神经胶质细胞中的作用。 脊柱动力学最后，我们将确定突触的维持是如何与脊柱运动性相关的， 由神经胶质过程调节。神经元连接的异常发育可能是导致 神经发育障碍此外，最近已经证明，异常的神经胶质细胞- 发育过程中的神经元相互作用可能会导致成年人的精神障碍。因此了解 突触形成过程中神经胶质-神经元相互作用的细胞和分子机制， 保养对健康有重要意义。

The long-term goal of this proposal is to understand the molecular and cellular mechanisms that regulate the development of cerebellar neuronal circuits. Dendritic spines, sites of synaptic input on many projection neurons such as the cerebellar purkinje cell are highly dynamic structures and their motility is developmentally regulated. The mechanisms that regulate spine dynamics over development are not known. Here, we will use multiphoton live imaging of neuronal structures in organotypic slices and in vivo, in conjunction with electron microscopy to study the mechanisms of synaptic maintenance. Our central hypothesis is that ensheathment by glial processes critically regulates dendritic spine motility andsynaptic stability. In the first aim we will characterize the development of Bergmann glia processes using static and dynamics imaging approaches. In the second aim we will test how spine dynamcis is regulated by glial ensehathment by measuring spine motility in genetic models with reduced glial ensehthment. In the third aim we will determine the role of EphA receptors and the ephrin ligands in glia-spine cross talk and regulation of spine dynamics. Finally, we will determine how synaptic mainetnance is related to spine motility and is regulated by glial processes. Abnormal development of neuronal connections can be the cause of neurodevelopmental disorders in humans. Moreover, recently it has been demonstrated that abnormal glial- neuron interactions during development might cause mental disorders in the adult. Therefore, understanding the cellular and molecular mechanisms of glial-neuron interactions during synapseformation and maintenance has important health significance.