Morphological homeostasis and adaptation in the Drosophila visual system

描述(申请人提供)：维持稳定的神经元形态和连接模式是维持正常神经回路功能的关键。这与视觉系统中的神经元特别相关，这些神经元高度动态，但仍保持稳定的连接模式，使视网膜中光感受器收集的视觉信息能够 通过视网膜定位图可靠地传递到后续的视神经节。然而，控制视觉系统中长期形态稳态的生理机制几乎完全是神秘的。果蝇高度刻板的视觉系统为剖析控制神经元形态依赖活动的维持和适应的分子和细胞机制提供了一个极好的系统。此外，强大的遗传工具、复杂的行为分析和成熟的体内成像技术使果蝇不仅成为研究神经元形态稳态控制机制的理想选择，也成为研究形态适应对神经回路活动和视觉动机苍蝇行为的贡献的方式的理想工具。这项提议将通过将神经元形态的定量测量与亚细胞分子定位模式的测量以及大规模神经活动模式和苍蝇行为的测量相关联来解决这些问题。此外，还将评估光感受器活性扰动的形态和行为后果，以及分子活性和定位模式的直接扰动的影响。这些实验将为了解果蝇视觉系统中控制形态稳态和适应的活动依赖机制提供一个分子框架。此外，这项提议将开始阐明神经形态和功能之间的关系，将细胞机制与大规模动物行为联系起来。

DESCRIPTION (provided by applicant): The maintenance of stable neuron morphologies and connectivity patterns is crucial for maintaining proper neural circuit function. This is particulary relevant for neurons in the visual system, which are highly dynamic and yet maintain stable connectivity patterns that allow visual information collected by photoreceptors in the retina to be reliably transmitted to subsequent visual ganglia by retinotopic mapping. However, the physiological mechanisms that control long-term morphological homeostasis in the visual system are almost completely mysterious. The highly-stereotyped visual system of the fruit fly, Drosophila melanogaster, provides an excellent system for dissecting the molecular and cellular mechanisms that control the activity-dependent maintenance and adaptation of neuron morphology. Moreover, powerful genetic tools, sophisticated behavioral assays, and well-established in vivo imaging techniques make Drosophila ideal not only for investigating the mechanisms that control neuron morphological homeostasis, but also for studying the manner in which morphological adaptations contribute to neural circuit activity and visually-motivated fly behaviors. This proposal will address these questions by correlating quantitative measurements of neuron morphology with measurements of sub- cellular molecular localization patterns, as well as measurements of large-scale neural activity patterns and fly behaviors. In addition, the morphological and behavioral consequences of photoreceptor activity perturbations, as well as the effects of direct perturbations of molecular activities and localization patterns, will be assessed. These experiments will provide a molecular framework for understanding the activity-dependent mechanisms that control morphological homeostasis and adaptation in the Drosophila visual system. Moreover, this proposal will begin to elucidate the relationship between neural form and function, linking cellular mechanisms to large-scale animal behavior.