Regulation /Dendritic Architecture in Nucleus Laminaris

描述（由申请人提供）：听觉脑干核层状核（NL）的树突在体内表现出对其传入纤维损伤的快速和高度选择性变性，表明神经元输入对于维持NL树突结构是必要的。这项研究的目标是利用电生理学和多光子成像技术来动态研究在同一细胞中随时间推移参与这一过程的细胞机制。利用该系统，将首先表征NL枝晶结构变化的时间过程和性质。然后，钙成像方法将与NL树突的形态计量学分析相结合，开始评估钙的变化是否在空间和/或时间上与树突结构的特定输入变化相关。还将进行药理学研究，以确定哪些分子是诱导NL树突局部变化所必需的。Rho GTPases，细胞骨架组织的重要调节因子，将特别感兴趣。最后，通过将输入替换为退化的NL树突，并评估它们是否能够重新生长，来评估树突结构变化的可逆性。

DESCRIPTION (provided by applicant): Dendrites of the auditory brainstem nucleus, nucleus laminaris (NL), exhibit rapid and highly selective degeneration in response to lesioning of their afferent fibers in vivo, suggesting that neuronal input is necessary for the maintenance of NL dendrite structure. The goal of the proposed research is to use electrophysiology and live, multi-photon imaging techniques to dynamically study the cellular mechanisms involved in this process, in the same cell over time. With this system, the time course and nature of the change in NL dendrite structure will first be characterized. Calcium imaging methods will then be used in combination with morphometric analysis of NL dendrites to begin assessing whether changes in calcium are spatially and/or temporally correlated with input-specific changes in dendrite structure. Pharmacological studies will also be conducted in order to determine which molecules are necessary for inducing localized changes in NL dendrites. The Rho GTPases, important regulators of cytoskeletal organization, will be of particular interest. Finally, the reversibility of the change in dendrite structure will be assessed by replacing input to degenerating NL dendrites and assessing whether they are able to re-grow.