CALCIUM MEDIATED PRESYNAPTIC HOMEOSTATIC PLASTICITY AT THE <EM >DROSOPHILA</EM> NMJ

At the presynaptic terminal of chemical synapses numerous calcium-dependent processes - synaptic vesicle (SV) release, SV recycling, and synaptic plasticity - occur side by side and must be coordinated. At the Drosophila neuromuscular junction (NMJ), a model for glutamatergic synapses, we previously found separate regulation of calcium-dependent SV release and recycling through division of labor between two voltage-gated calcium channels (VGCCs). The Ca_v2 homolog cacophony (cac) mediates evoked SV release at active zones, while the Ca_v1 homolog DmCa1D, localized outside active zones, augments SV recycling and short-term plasticity. The calcium pump PMCA isolates these functions.
We now report that both, PMCA and DmCa1D are also required for the initiation of presynaptic homeostatic plasticity (PHP), which adjusts release probability (P_r) and comprises separable initiation and maintenance phases. During PHP initiation P_r increases via upregulation of cac channels in active zones. Combining Drosophila genetics, electrophysiology and imaging techniques we test whether signaling downstream of Ca_v1 and PMCA is required for PHP maintenance.
A key question is whether synapses can re-initiate PHP in response to repeated perturbations. This requires resetting active zone cac numbers and maintaining increased P_r via alternative mechanisms. Candidate mechanisms for retaining increased P_r during PHP maintenance involve ER calcium-signaling and regulation of plasma membrane (PM)-ER interactions. First data indicate that tuning calcium induced calcium release through ryanodine receptors and/or store operated calcium entry via STIM-Orai channels at newly formed PM-ER contacts may sustain P_r during PHP maintenance while restoring PMCA and Ca_v1's ability to scale up P_r.