The neural basis for aging-dependent decline in taste function

项目摘要 化学感觉处理的缺陷与健康的衰老以及许多神经退行性疾病有关。 包括阿尔茨海默病（AD）的疾病。在许多情况下，化学感觉缺陷是 神经退行性疾病，了解这些变化的机制基础可能会提供深入了解 与衰老和神经退化相关的基本功能障碍。基因和生理 化学感觉神经元的可及性及其定义的高阶处理中心提供了独特的 有机会研究衰老相关过程对神经功能的影响，包括感觉 反应性、可塑性和突触连接性。果蝇，黑腹果蝇， 用于研究化学感觉、衰老和与衰老相关的病理学，但衰老对化学感觉的影响 在这个模型中，特别是在味道方面，仍然没有被探索。一个大型的基因工具箱， 功能成像允许味觉回路的细胞类型特异性操纵。许多型号的AD 在果蝇中发展，主要表现为AD的两个标志：淀粉样蛋白β（Aβ）介导的毒性和 由Tau蛋白的过度磷酸化引起的Tau病。我的初步发现表明 感知和味觉记忆随着年龄的增长而恶化，并且这在AD的苍蝇模型中加剧。来，我来 研究模型中与年龄相关的味觉和味觉记忆下降的生理和分子基础 自然衰老和病理衰老。这些实验建立在我在化学感觉处理方面的专业知识基础上， 功能成像，同时提供老化和基因组方法的培训。

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.