Spontaneous glutamate release-driven NMDA receptor activity exerts a strong influence on synaptic homeostasis. However, the properties of Ca(2+) signals that mediate this effect remain unclear. Here, using hippocampal neurons labeled with the fluorescent Ca(2+) probes Fluo-4 or GCAMP5, we visualized action potential-independent Ca(2+) transients in dendritic regions adjacent to fluorescently labeled presynaptic boutons in physiological levels of extracellular Mg(2+). These Ca(2+) transients required NMDA receptor activity, and their propensity correlated with acute or genetically induced changes in spontaneous neurotransmitter release. In contrast, they were insensitive to blockers of AMPA receptors, L-type voltage-gated Ca(2+) channels, or group I mGluRs. However, inhibition of Ca(2+)-induced Ca(2+) release suppressed these transients and elicited synaptic scaling, a process which required protein translation and eukaryotic elongation factor-2 kinase activity. These results support a critical role for Ca(2+)-induced Ca(2+) release in amplifying NMDA receptor-driven Ca(2+) signals at rest for the maintenance of synaptic homeostasis.
Keywords: Ca2+ induced Ca2+ release; NMDA receptor signaling; homeostatic plasticity; mouse; neuroscience; rat; spontaneous neurotransmitter release.