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Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition

  1. Charles T Anderson Is a corresponding author
  2. Manoj Kumar
  3. Shanshan Xiong
  4. Thanos Tzounopoulos Is a corresponding author
  1. University of Pittsburgh, United States
Research Article
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Cite as: eLife 2017;6:e29893 doi: 10.7554/eLife.29893

Abstract

In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

Article and author information

Author details

  1. Charles T Anderson

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    charles.anderson@hsc.wvu.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Manoj Kumar

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shanshan Xiong

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Thanos Tzounopoulos

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    thanos@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-4583-145X

Funding

National Institute on Deafness and Other Communication Disorders (R01-DC007905)

  • Thanos Tzounopoulos

National Institute on Deafness and Other Communication Disorders (F32-DC013734)

  • Charles T Anderson

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

Ethics

Animal experimentation: Animal experimentation: Animals were handled, anesthetized and sacrificed according to methods approved by the University of Pittsburgh Institutional Animal Care and Use Committee. The approved IACUC protocol numbers that were employed for this study were: #14125118 and #14094011.

Reviewing Editor

  1. Andrew J King, Reviewing Editor, University of Oxford, United Kingdom

Publication history

  1. Received: June 23, 2017
  2. Accepted: September 4, 2017
  3. Accepted Manuscript published: September 9, 2017 (version 1)

Copyright

© 2017, Anderson et al.

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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