title: Spontaneous neurotransmission signals through store-driven Ca(2+) transients to maintain synaptic homeostasis.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Austin L
authors.initials: AL
authors.lastname: Reese
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006706:Homeostasis; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium
keywords: Ca2+ induced Ca2+ release; NMDA receptor signaling; homeostatic plasticity; mouse; neuroscience; rat; spontaneous neurotransmitter release