4.8 Article

Spontaneous neurotransmission signals through store-driven Ca2+ transients to maintain synaptic homeostasis

Journal

ELIFE
Volume 4, Issue -, Pages -

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ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.09262

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  1. National Institutes of Health (NIH) [MH066198]
  2. National Institute of Neurological Disorders and Stroke (NINDS) [T32 NS069562]

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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.

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