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

  1. Austin L Reese
  2. Ege T Kavalali  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States

Abstract

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.

Article and author information

Author details

  1. Austin L Reese

    Departments of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ege T Kavalali

    Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    ege.kavalali@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Indira M Raman, Northwestern University, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the UT Southwestern Medical Center (APN# 0866-06-05-1)

Version history

  1. Received: June 6, 2015
  2. Accepted: July 24, 2015
  3. Accepted Manuscript published: July 24, 2015 (version 1)
  4. Version of Record published: August 13, 2015 (version 2)

Copyright

© 2015, Reese & Kavalali

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Austin L Reese
  2. Ege T Kavalali
(2015)
Spontaneous neurotransmission signals through store-driven Ca2+ transients to maintain synaptic homeostasis
eLife 4:e09262.
https://doi.org/10.7554/eLife.09262

Share this article

https://doi.org/10.7554/eLife.09262

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