TY - JOUR
T1 - Spontaneous neurotransmission signals through store-driven Ca2+ transients to maintain synaptic homeostasis
AU - Reese, Austin L.
AU - Kavalali, Ege T.
N1 - Publisher Copyright:
© 2015, Reese and Kavalali.
PY - 2015/7/24
Y1 - 2015/7/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84939512053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939512053&partnerID=8YFLogxK
U2 - 10.7554/eLife.09262.001
DO - 10.7554/eLife.09262.001
M3 - Article
C2 - 26208337
AN - SCOPUS:84939512053
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - JULY2015
M1 - e09262
ER -