Morphological homeostasis and adaptation in the Drosophila visual system

描述（由申请人提供）：维持稳定的神经元形态和连接模式对于维持适当的神经回路功能至关重要。这与视觉系统中的神经元特别相关，视觉系统中的神经元是高度动态的，但仍保持稳定的连接模式，使得视网膜中的光感受器收集的视觉信息能够被传递到视网膜中。 通过视网膜定位图可靠地传递到随后的视觉神经节。然而，控制视觉系统长期形态稳态的生理机制几乎是完全神秘的。果蝇的高度定型的视觉系统，果蝇，提供了一个很好的系统，解剖的分子和细胞机制，控制活动依赖性的维护和适应的神经元形态。此外，强大的遗传工具，复杂的行为分析，以及完善的体内成像技术，使果蝇的理想不仅调查的机制，控制神经元形态的稳态，但也为研究的方式，形态适应有助于神经回路活动和视觉动机的苍蝇行为。该提案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，光感受器活动扰动的形态和行为后果，以及分子活动和定位模式的直接扰动的影响，将进行评估。这些实验将为理解控制果蝇视觉系统形态稳态和适应的活动依赖性机制提供一个分子框架。此外，这项建议将开始阐明神经形式和功能之间的关系，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.