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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH074231-02
Application #
7122032
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Curvey, Mary F
Project Start
2005-09-06
Project End
2008-09-05
Budget Start
2006-09-06
Budget End
2007-09-05
Support Year
2
Fiscal Year
2006
Total Cost
$52,048
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Murakami, Satoshi; Dan, Chuntao; Zagaeski, Brendan et al. (2010) Optimizing Drosophila olfactory learning with a semi-automated training device. J Neurosci Methods 188:195-204