Convergent deficits of memory consolidation in aged and sleep-deprived Drosophila

Sleep has been found to support memory consolidation in a spectrum of model organisms and the human being. With increasing organismal age, however, sleep fragments and memory consolidation attenuates. By which mechanisms and at what level the aging process intersects with memory consolidation and sleep remains largely unclear. In aging Drosophila fruit flies, consolidation of classical conditioned olfactory memory becomes ineficient and the number of sleep episodes increases. We in A08 will use this model to investigate this intersection concentrating on a brain-wide metaplastic change of synapses (increase of presynaptic active zone sizes) we recently found in aged flies. When we mimicked this meta-plasticity genetically (by elevating the gene dose of active zone scaffold proteins), memory consolidation decreased and the number of sleep episodes increased, similarly to aged flies. Here, we will reprogram presynaptic plasticity within relevant neuronal populations in order to learn about the synaptic and circuitry principles connecting aging, sleep and memory consolidation. Thus, we will measure how behavioral responses, such as olfactory aversive learning and sleep, are affected by opto−physiological methods combined with genetic manipulation. In addition, dorsal paired medial neurons will be specifically analyzed, as they have been previously shown to promote olfactory memory consolidation, and their artificial stimulation influences sleep and can compensate for age-induced deficits of consolidation. A08 will also use spermidine feeding as a protective paradigm, found to alleviate age-induced effects on memory consolidation. This strategy should help us to further separate causal entities from epiphenomena at the intersection of age, memory consolidation and sleep.