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s Similarly Alters Pre- and Postsynaptic Mechanisms Modulating Neurotransmission
1 Biology, University of Utah, Salt Lake City, UT, USA; Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA
2 Biological Sciences, Vanderbilt University, Nashville, TN, USA; Center for Molecular Neuroscience, Vanderbilt University, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: kendal.broadie{at}vanderbilt.edu.
Constitutive activation of G
s in the Drosophila brain abolishes associative learning, a behavioral disruption far worse than that observed in any single cAMP metabolic mutant, suggesting that Gs is essential for synaptic plasticity. The intent of this study was to examine the role of Gs in regulating synaptic function by targeting constitutively active Gs to either pre- or postsynaptic cells, and by examining loss-of-function Gs mutants (dgs), at the glutamatergic neuromuscular junction (NMJ) model synapse. Surprisingly, both loss of Gs and activation of Gs in either pre- or postsynaptic compartment similarly increased basal neurotransmission, decreased short-term plasticity (facilitation and augmentation), and abolished post-tetanic potentiation. Elevated synaptic function was specific to an evoked neurotransmission pathway since both spontaneous synaptic vesicle fusion frequency and amplitude were unaltered in all mutants. In the postsynaptic cell, the glutamate receptor field was regulated by Gs activity; based on immunocytochemical studies, GluRIIA receptor subunits were dramatically downregulated (>75% decrease) in both loss and constitutive active Gs genotypes. In the presynaptic cell, the synaptic vesicle cycle was regulated by Gs activity; based on FM1-43 dye imaging studies, evoked vesicle fusion rate was increased in both loss and constitutively active Gs genotypes. An important conclusion of this study is that both increased and decreased Gs activity very similarly alters pre- and postsynaptic mechanisms. A second important conclusion is that Gs activity induces transynaptic signaling; targeted Gs activation in the presynapse downregulates postsynaptic GluRIIA receptors, whereas targeted Gs activation in the postsynapse enhances presynaptic vesicle cycling.
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