Spontaneous glutamate release-driven NMDA receptor activity exerts a strong influence on synaptic homeostasis. However, the properties of Ca2+ signals that mediate this effect remain unclear. Here, using hippocampal neurons labeled with the fluorescent Ca2++ probes Fluo-4 or GCAMP5, we visualized action potential-independent Ca2++ transients in dendritic regions adjacent to fluorescently labeled presynaptic boutons in physiological levels of extracellular Mg2+. These Ca2++ 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 Ca2++ channels, or group I mGluRs. However, inhibition of Ca2++-induced Ca2++ 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 Ca2++-induced Ca2++ release in amplifying NMDA receptor-driven Ca2++ signals at rest for the maintenance of synaptic homeostasis.
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)