Fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of GABAergic neurons
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.
Article and author information
Author details
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.
Reviewing Editor
- Michael Schmid, Newcastle University, United Kingdom
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).
Version history
- Received: October 11, 2019
- Accepted: May 24, 2020
- Accepted Manuscript published: May 26, 2020 (version 1)
- 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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