Calcium permeability–enhancing mutations in GluRIIC suppress sustained presynaptic homeostatic plasticity triggered by loss of GluRIIA

Presynaptic homeostatic plasticity (PHP) stabilizes neural circuits by adjusting synaptic strength when faced with disturbances in postsynaptic activity. Despite identification of many genes and mechanisms required for PHP, the underlying trigger mechanisms remain elusive. Loss of GluRIIA, one of five glutamate receptor subunits at the Drosophila neuromuscular junction (NMJ), reduces quantal size and synaptic calcium influx and triggers a sustained PHP. Two common features of genetic manipulations that lead to the activation of this form of PHP are a drop in synaptic calcium influx and a reduction in quantal size; however, it is not clear that either of these features is absolutely necessary for PHP. We have generated a glutamate receptor transgene with mutations in the pore, which can largely restore calcium influx in GluRIIA ^−/− mutant larvae without affecting quantal size. We find that restoration of calcium influx in GluRIIA ^−/− mutant larvae blocks PHP without any detectable changes in synaptic structure. Our findings, therefore, indicate that a reduction in synaptic calcium influx is necessary for triggering and/or maintenance of the sustained PHP at the NMJ, a model that may be extendable to the vertebrate NMJ and neuron–neuron synapses.