ResearchCrossroads

Summary
DESCRIPTION (provided by applicant): The long-term objective is to identify novel mechanisms regulating adult central synaptic structural plasticity in vivo. Synapses appear dynamic in adult Drosophila brain. In addition, hyper-activating neurons, or over-expressing an active Raf, either throughout or after development, seems to induce ectopic synapses. Adult central synaptic structural dynamics will be investigated using long-term multi-photon confocal imaging in the brains of live whole flies. Dependence on neural activity will be examined while genetically hyper-activating or silencing the imaged neurons post-developmentally. Molecular mechanisms regulating adult central synaptic structure will be explored by over-expressing candidate genes, such as those in the mitogen-activated kinase pathway, and, if time permits, screening fly lines randomly over-expressing genes in adult brains, selecting those showing abnormal patterns of fluorescent pre- and post-synaptic markers. Identified genes will be cloned and their loss-of-function phenotypes will be characterized using RNAi. Understanding and harnessing these molecular mechanisms will contribute to the prevention and treatment of mental disorders, which are often associated with the disruption of synaptic structure.
Anticipated Outcomes
Biochemical Pathway Brain Brain imaging Candidate Disease Gene Clone Diptera Drosophila Flying body movement Gene Expression Regulation Genes MAP kinase activity Mental disorders Neurons Phenotype Photons Plasticity Pressure- physical agent RNA Interference Synapses

Principal Investigator	Chuntao Dan
Co-Principal Investigator(s)
Recipient Organization	HARVARD UNIVERSITY
Granting Organization	National Institute of Mental Health(NIMH)

Reference	Dates	Fiscal Year	Funded Amount
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