Dynamics of cerebellar Purkinje cell dendrites

这项提议的长期目标是了解调节细胞周期的分子和细胞机制。 小脑神经元回路的发育。树突棘，突触在许多投射中的输入部位 像小脑浦肯野细胞这样的神经元是高度动态的结构，它们的运动性是 发育调节的。在发育过程中调节脊柱动力的机制不是 为人所知。在这里，我们将使用多光子实时成像的神经元结构在器官切片和活体，在 结合电子显微镜研究突触维持的机制。我们的中央 假设神经胶质突起的包膜对树突棘的运动和突触具有重要的调节作用。 稳定性。在第一个目标中，我们将用静态和静态来表征Bergmann胶质细胞突起的发展 动力学成像方法。在第二个目标中，我们将测试神经胶质是如何调节脊柱动力的。 在胶质细胞植入减少的遗传模型中通过测量脊柱运动性来获得植入。第三个目标 我们将确定EphA受体和肾上腺素配体在神经胶质细胞-脊柱串扰和调节 脊椎动力学。最后，我们将确定突触维持如何与脊柱运动有关，以及 受神经胶质细胞的调节。神经元连接的异常发育可能是 人类的神经发育障碍。此外，最近有研究表明，异常胶质细胞- 神经元在发育过程中的相互作用可能会导致成年人的精神障碍。因此，理解 突触形成过程中胶质细胞-神经元相互作用的细胞和分子机制 养生具有重要的健康意义。

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.