1. Neuroscience
Download icon

Single synapse evaluation of the postsynaptic NMDA receptors targeted by evoked and spontaneous neurotransmission

  1. Austin L Reese
  2. Ege T Kavalali  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
Research Article
  • Cited 21
  • Views 2,020
  • Annotations
Cite this article as: eLife 2016;5:e21170 doi: 10.7554/eLife.21170


Recent studies indicate that within individual synapses spontaneous and evoked release processes are segregated and regulated independently. In the hippocampus, earlier electrophysiological recordings suggested that spontaneous and evoked glutamate release can activate separate groups of postsynaptic NMDA receptors with limited overlap. However, it is still unclear how this separation of NMDA receptors is distributed across individual synapses. In a previous paper (Reese and Kavalali, 2015) we showed that NMDA receptor mediated spontaneous transmission signals to the postsynaptic protein translation machinery through Ca2+-induced Ca2+ release. Here, we show that in rat hippocampal neurons although spontaneous and evoked glutamate release driven NMDA receptor mediated Ca2+ transients often occur at the same synapse, these two signals do not show significant correlation or cross talk.

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

    Departments of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1777-227X


National Institute of Mental Health

  • Ege T Kavalali

National Institute of Neurological Disorders and Stroke

  • Austin L Reese
  • Ege T Kavalali

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: 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).

Reviewing Editor

  1. Indira M Raman, Northwestern University, United States

Publication history

  1. Received: September 1, 2016
  2. Accepted: November 23, 2016
  3. Accepted Manuscript published: November 24, 2016 (version 1)
  4. Version of Record published: December 9, 2016 (version 2)
  5. Version of Record updated: December 14, 2016 (version 3)


© 2016, 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.


  • 2,020
    Page views
  • 623
  • 21

Article citation count generated by polling the highest count across the following sources: Scopus, PubMed Central, Crossref.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    2. Neuroscience
    Alicia Tapias et al.
    Research Article Updated

    Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (ransformation/translation domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism, and epilepsy, with unknown mechanism. Here we show that Trrap deletion in Purkinje neurons results in neurodegeneration of old mice. Integrated transcriptomics, epigenomics, and proteomics reveal that TRRAP via SP1 conducts a conserved transcriptomic program. TRRAP is required for SP1 binding at the promoter proximity of target genes, especially microtubule dynamics. The ectopic expression of Stathmin3/4 ameliorates defects of TRRAP-deficient neurons, indicating that the microtubule dynamics is particularly vulnerable to the action of SP1 activity. This study unravels a network linking three well-known, but up-to-date unconnected, signaling pathways, namely TRRAP, HAT, and SP1 with microtubule dynamics, in neuroprotection.

    1. Neuroscience
    Lawrence Huang et al.
    Tools and Resources

    Fluorescent calcium indicators are often used to investigate neural dynamics, but the relationship between fluorescence and action potentials (APs) remains unclear. Most APs can be detected when the soma almost fills the microscope's field of view, but calcium indicators are often used to image populations of neurons, necessitating a large field of view, generating fewer photons per neuron, and compromising AP detection. Here we characterized the AP-fluorescence transfer function in vivo for 48 layer 2/3 pyramidal neurons in primary visual cortex, with simultaneous calcium imaging and cell-attached recordings from transgenic mice expressing GCaMP6s or GCaMP6f. While most APs were detected under optimal conditions, under conditions typical of population imaging studies only a minority of 1AP and 2AP events were detected (often <10% and ~20-30%, respectively), emphasizing the limits of AP detection under more realistic imaging conditions.