Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition
- University of Pittsburgh, United States
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
Thanos Tzounopoulos
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
- Andrew J King, University of Oxford, United Kingdom
Publication history
- Received: June 23, 2017
- Accepted: September 4, 2017
- Accepted Manuscript published: September 9, 2017 (version 1)
- Version of Record published: October 10, 2017 (version 2)
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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Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition
eLife 6:e29893.
https://doi.org/10.7554/eLife.29893
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