The neural basis for aging-dependent decline in taste function

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.