Jeffrey Dason, Department of Biomedical Sciences, University of Windsor Activity-dependent cholesterol redistribution is required for synaptic growth Synaptic plasticity is a fundamental property of neurons that allows their ability to transmit information to change with experience. Numerous studies have examined how synaptic plasticity is regulated by protein–protein interactions and changes in the expression and activation of various proteins. In contrast, the roles of lipids in synaptic plasticity have been less studied. Increasing evidence suggests that the lipid content of neuronal membranes does not remain constant and is altered by synaptic activity. The Drosophila larval neuromuscular junction is a well-established model system for studying synaptic growth and shares the basic molecular components found at most synapses. We generated transgenic flies that express the cholesterol binding D4H domain of Perfringolysin O toxin fused to GFP and found increased levels of cholesterol in presynaptic terminals of glutamatergic Drosophila neuromuscular junctions following periods of increased synaptic activity. We found that cholesterol is required for both synaptic growth and activity-dependent synaptic growth. Examination of several mutant and transgenic larvae reveal that cholesterol is likely regulating synaptic growth through the cAMP-PKA kinase signaling pathway. Collectively, our data demonstrates that cholesterol redistribution occurs in response to synaptic activity and that it plays a key role in development and activity-dependent synaptic plasticity.
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