The balance of excitation and inhibition in the nervous system appears to be a key factor in the etiology of many neurodegenerative diseases. However, the mechanisms that control this balance are poorly understood. Recent studies suggest that homeostatic mechanisms monitor and regulate the levels of cellular excitation in the nervous system. A model for the homeostatic regulation of neuronal excitability has been developed at a glutamatergic synapse in Drosophila that parallels models of synaptic homeostasis in the vertebrate central and peripheral nervous systems. This proposal details experiments designed to elucidate the properties of synaptic homeostasis in Drosophila. The approach will be twofold. First, electrophysiological techniques will be conducted to characterize the time-course and reversibility of synaptic homeostasis. To do this, the GAL4-UAS system will be used, which will allow conditional disruption of muscle excitation, and therefore, conditional activation of homeostatic signaling. Second, a genome-scale, reverse genetics screen to identify genes involved in homeostatic signaling will be performed. To conduct this screen, a library of 7260 Drosophila dsRNA molecules is available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS049694-02
Application #
6946808
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Talley, Edmund M
Project Start
2004-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Frank, C Andrew; Pielage, Jan; Davis, Graeme W (2009) A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels. Neuron 61:556-69
Frank, C Andrew; Kennedy, Matthew J; Goold, Carleton P et al. (2006) Mechanisms underlying the rapid induction and sustained expression of synaptic homeostasis. Neuron 52:663-77