Fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of GABAergic neurons

  1. Abhishek De
  2. Yasmine El-Shamayleh
  3. Gregory D Horwitz  Is a corresponding author
  1. University of Washington, United States
  2. Columbia University, United States

Abstract

Reversible optogenetic neural inactivation techniques are valuable for linking neural activity and behavior but they have serious limitations in macaques. To achieve powerful and temporally precise neural inactivation, we used an adeno-associated viral (AAV) vector carrying the channelrhodopsin-2 gene under the control of a Dlx5/6 enhancer, which restricts expression to GABAergic neurons. We tested this approach in the primary visual cortex, an area where neural inactivation leads to interpretable behavioral deficits. Optical stimulation modulated spiking activity and reduced visual sensitivity profoundly in the region of space represented by the stimulated neurons. Rebound firing, which can have unwanted effects on neural circuits following inactivation, was not observed, and the efficacy of the optogenetic manipulation on behavior was maintained across >1000 trials. We conclude that this inhibitory cell-type specific optogenetic approach is a powerful and spatiotemporally precise neural inactivation tool with broad utility for probing the functional contributions of different cortical areas in macaques.

Data availability

All data have been uploaded to https://github.com/horwitzlab.

The following data sets were generated

Article and author information

Author details

  1. Abhishek De

    Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yasmine El-Shamayleh

    Department of Neuroscience & Zuckerman Institute, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gregory D Horwitz

    Department of Physiology and Biophysics, Washington National Primate Research Center, University of Washington, Seattle, United States
    For correspondence
    ghorwitz@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5130-5259

Funding

National Eye Institute (EY030441)

  • Gregory D Horwitz

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

Ethics

Animal experimentation: Surgical procedures, experimental protocols and animal care conformed to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at the University of Washington (IACUC protocol #4167-01).

Reviewing Editor

  1. Michael Schmid, Newcastle University, United Kingdom

Publication history

  1. Received: October 11, 2019
  2. Accepted: May 24, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Version of Record published: July 1, 2020 (version 2)

Copyright

© 2020, De 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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  1. Abhishek De
  2. Yasmine El-Shamayleh
  3. Gregory D Horwitz
(2020)
Fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of GABAergic neurons
eLife 9:e52658.
https://doi.org/10.7554/eLife.52658
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