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Intersection of active zone plasticity and memory formation in the aging mushroom body

All animals form memories to adapt their behavior in a context-dependent manner. With increasing age, however, forming new memories becomes less efficient, due to a largely unknown etiology. Searching for a mechanistic basis of age-induced memory impairment (AMI), we identified a brain-wide, age-associated upshift in the ultrastructural size and release function of presynaptic active zones (AZs) in the fruit fly Drosophila. This phenomenon (we called “RAMP-UP”) was absent from aged animals being pharmacologically protected from AMI, while genetically provoked RAMP-UP eliminated memory formation in young animals. Our data provoke the hypothesis that RAMP-UP narrows the synaptic plasticity space by adjusting the efficacy of memory formation to increasing lifetime and experience, with the functional and structural AZ status operating as a major “adjustment screw”. Based on our previous analysis of principal AZ organization, we start by subjecting the AZ to a rigorous analysis concerning its role in olfactory memory formation within the mushroom body. Based on this, we will test directly whether AZ RAMP-UP interferes with plasticity processes encoding aversive memories within the mushroom body. This work will provide a basis to study information storage strategies in an aging and experience-forming brain.