Asymmetric effects of activating and inactivating cortical interneurons

  1. Elizabeth AK Phillips
  2. Andrea R Hasenstaub  Is a corresponding author
  1. University of California San Francisco, United States

Abstract

Bidirectional manipulations-activation and inactivation-are widely used to identify the functions supported by specific cortical interneuron types. Implicit in much of this work is the notion that tonic activation and inactivation will both produce valid, internally consistent insights into interneurons' computational roles. Here, using single-unit recordings in auditory cortex of awake mice, we show that this may not generally hold true. Optogenetically manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+) interneurons while recording tone-responses showed that Sst+ inactivation increased response gain, while Pvalb+ inactivation weakened tuning and decreased information transfer, implying that these neurons support delineable computational functions. But activating Sst+ and Pvalb+ interneurons revealed no such differences. We used a simple network model to understand this asymmetry, and showed how relatively small changes in key parameters, such as spontaneous activity or strength of the light manipulation, determined whether activation and inactivation would produce consistent or paradoxical conclusions regarding interneurons' computational functions.

Article and author information

Author details

  1. Elizabeth AK Phillips

    Center for Integrative Neuroscience and Coleman Memorial Laboratory, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrea R Hasenstaub

    Center for Integrative Neuroscience and Coleman Memorial Laboratory, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, United States
    For correspondence
    andrea.hasenstaub@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3998-5073

Funding

Esther A. and Joseph Klingenstein Fund (Klingenstein-Simons Fellowship Award)

  • Andrea R Hasenstaub

John C. and Edward Coleman Memorial Fund

  • Andrea R Hasenstaub

Hearing Research Institute

  • Andrea R Hasenstaub

National Institutes of Health (RO1, DC014101)

  • Andrea R Hasenstaub

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

Ethics

Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committee at the University of California, San Francisco under protocol AN111186.

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: June 2, 2016
  2. Accepted: October 9, 2016
  3. Accepted Manuscript published: October 10, 2016 (version 1)
  4. Version of Record published: November 25, 2016 (version 2)

Copyright

© 2016, Phillips & Hasenstaub

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. Elizabeth AK Phillips
  2. Andrea R Hasenstaub
(2016)
Asymmetric effects of activating and inactivating cortical interneurons
eLife 5:e18383.
https://doi.org/10.7554/eLife.18383

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