Regulation /Dendritic Architecture in Nucleus Laminaris

描述(申请人提供)：听性脑干核层状核(NL)的树突在体内对其传入纤维的损伤表现出快速和高度选择性的退化，表明神经元的输入对于NL树突结构的维持是必要的。这项研究的目标是利用电生理学和活的多光子成像技术，随着时间的推移，在同一细胞中动态研究参与这一过程的细胞机制。利用这一系统，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树突的形态计量分析相结合，以开始评估钙的变化是否在空间和/或时间上与输入特定于树突结构的变化相关。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 GTP酶是细胞骨架组织的重要调节者，将特别引起人们的兴趣。最后，将通过替换退化的NL树枝晶的输入并评估它们是否能够重新生长来评估树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.