This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In previous work, we have defined a role for Notch function in the integrity of the adult nervous system of Drosophila. Flies in which Notch is conditionally compromised display neurodegenerative defects that included a reduced life span, uncoordinated flight, and an impairment of long-term memory. Experiments were performed in adult flies after the nervous system was fully developed and non-mitotic. Our hypothesis is that Notch is necessary for neuroplasticity in differentiated neurons. Plasticity in this context is defined as the acquisition or maintenance of neural structures (dendrites, axons, synapses) in order to functionally deal with the individual organism's unique set of life experiences. Plastic regions of the brain would be expected to have a dynamic neuroarchitecture depending on such conditions as sensory inputs from environments rich in stimuli, attrition of unused neural connections, or injury. Drosophila is an ideal model system for these investigations for two reasons. First, the molecular pathways contributing to Drosophila development and aging can be dissected using powerful genetic tools to assay the important functional genes. Second, many of these critical pathways are conserved through evolution from insects to vertebrates, and Drosophila has made substantial contributions to our current understanding of signaling pathways and disease pathologies in humans. Thus, we propose to investigate the hypothesis that the major role of Notch signaling in the adult nervous system is to contribute to plastic functions that include memory, and that we can use Drosophila to model important aspects of Alzheimer s disease.
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