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Science 326 (5956): 1127-1130

Copyright © 2009 by the American Association for the Advancement of Science

The Schizophrenia Susceptibility Gene dysbindin Controls Synaptic Homeostasis

Dion K. Dickman, and Graeme W. Davis*

Abstract: The molecular mechanisms that achieve homeostatic stabilization of neural function remain largely unknown. To better understand how neural function is stabilized during development and throughout life, we used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans. We found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurological disease.

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: graeme.davis{at}ucsf.edu


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