The neural basis for aging-dependent decline in taste function

项目总结 化学感觉处理的缺陷与健康的衰老以及许多神经退行性变有关。 包括阿尔茨海默病(AD)在内的各种疾病。在许多情况下，化学感觉缺陷预示着 神经退行性疾病，并了解这些变化的机制基础可能有助于洞察 与衰老和神经退化相关的基本功能障碍。遗传学和生理学 化学感觉神经元及其定义的更高阶处理中心的可及性提供了独特的 研究与衰老相关的过程对神经功能，包括感觉的影响的机会 反应性、可塑性和突触连通性。果蝇，黑腹果蝇，是一个强大的模型 用于研究化学感觉、衰老和衰老相关的病理，但衰老对化学感觉的影响 在这种模式下仍然很大程度上没有被探索，特别是在品味方面。一个大型遗传工具包，结合了 功能成像允许对味觉回路进行细胞类型的特定操作。AD BE的多种型号 在果蝇中发生，主要表现为AD的两个特征：淀粉样β蛋白(Aβ)介导的毒性和 由于Tau蛋白过度磷酸化而引起的肌萎缩侧索硬化。我的初步研究结果显示， 知觉和味觉记忆随着年龄的增长而恶化，这在阿尔茨海默病的苍蝇模型中加剧。在这里，我会 研究增龄相关味觉和味觉记忆减退的生理和分子基础 自然衰老和病理性衰老。这些实验建立在我在化学传感处理方面的专业知识和 功能成像，同时提供衰老和基因组方法方面的培训。

PROJECT SUMMARY Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders including Alzheimer’s Disease (AD). In many cases, chemosensory deficits are harbingers of neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into fundamental dysfunction associated with aging and neurodegeneration. The genetic and physiological accessibility of chemosensory neurons and their defined higher order processing centers provide a unique opportunity to investigate the effects of aging-related processes on neural function, including sensory responsiveness, plasticity, and synaptic connectivity. The fruit fly, Drosophila melanogaster, is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging on chemosensation remain largely unexplored in this model, particularly with respect to taste. A large genetic toolkit combined with functional imaging allow for cell-type specific manipulation of taste circuits. Numerous models of AD been developed in Drosophila that largely phenocopy two hallmarks of AD: amyloid beta (Aβ)-mediated toxicity and tauopathy caused by hyperphosphorylation of the Tau protein. My preliminary findings reveal that taste perception and taste memory deteriorate with age, and this is exacerbated in a fly model of AD. Here, I will examine the physiological and molecular basis for age-associated reduction in taste and taste memory in models of natural and pathological aging. These experiments build on my expertise in chemosensory processing and functional imaging, while providing training in aging and genomic approaches.