Regulation /Dendritic Architecture in Nucleus Laminaris

描述（由申请人提供）：听觉脑干核的树突，即板状核（NL），在体内对其传入纤维的损伤作出反应时表现出快速和高度选择性的变性，这表明神经元输入对于维持NL树突结构是必要的。拟议研究的目标是使用电生理学和实时多光子成像技术来动态研究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。然后将钙成像方法与NL树突的形态测定分析结合使用，以开始评估钙的变化是否与树突结构的输入特异性变化在空间和/或时间上相关。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 GTP酶是细胞骨架组织的重要调节剂，将特别令人感兴趣。最后，将通过替换退化NL枝晶的输入并评估它们是否能够重新生长来评估枝晶结构变化的可逆性。

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.