Genetic Control of Synaptic Structure in the Adult Brain.

描述（由申请人提供）：长期目标是确定体内调节成人中枢突触结构可塑性的新机制。成年果蝇脑中的突触是动态的。此外，过度激活的神经元，或过度表达一个活跃的Raf，无论是在整个或之后的发展，似乎诱导异位突触。成年中枢突触结构动力学将使用长期多光子共聚焦成像在活的整个苍蝇的大脑中进行研究。在遗传上过度激活或沉默发育后成像的神经元时，将检查对神经活动的依赖性。调节成人中央突触结构的分子机制将探索过度表达的候选基因，如在丝裂原活化激酶途径，如果时间允许，筛选飞线随机过度表达的基因在成人大脑中，选择那些显示异常模式的荧光前和突触后标记。将克隆鉴定的基因，并使用RNAi表征其功能丧失表型。理解和利用这些分子机制将有助于预防和治疗精神障碍，这通常与突触结构的破坏有关。

DESCRIPTION (provided by applicant): The long-term objective is to identify novel mechanisms regulating adult central synaptic structural plasticity in vivo. Synapses appear dynamic in adult Drosophila brain. In addition, hyper-activating neurons, or over-expressing an active Raf, either throughout or after development, seems to induce ectopic synapses. Adult central synaptic structural dynamics will be investigated using long-term multi-photon confocal imaging in the brains of live whole flies. Dependence on neural activity will be examined while genetically hyper-activating or silencing the imaged neurons post-developmentally. Molecular mechanisms regulating adult central synaptic structure will be explored by over-expressing candidate genes, such as those in the mitogen-activated kinase pathway, and, if time permits, screening fly lines randomly over-expressing genes in adult brains, selecting those showing abnormal patterns of fluorescent pre- and post-synaptic markers. Identified genes will be cloned and their loss-of-function phenotypes will be characterized using RNAi. Understanding and harnessing these molecular mechanisms will contribute to the prevention and treatment of mental disorders, which are often associated with the disruption of synaptic structure.