Asymmetric effects of activating and inactivating cortical interneurons
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
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
- Naoshige Uchida, Harvard University, United States
Version history
- Received: June 2, 2016
- Accepted: October 9, 2016
- Accepted Manuscript published: October 10, 2016 (version 1)
- 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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