Spatiotemporal constraints on optogenetic inactivation in cortical circuits
- Baylor College of Medicine, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- Tsinghua University, China
- CNRS-UMR8119, France
Abstract
Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks ('paradoxical effect'). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of in vivo optogenetics experiments.
Data availability
Rosa26-CAG-LNL-GtACR1-ts-FRed-Kv2.1 mice are available at The Jackson Laboratory (stock #033089). Electrophysiology data and code used are available at Github (https://github.com/NuoBCM/PhotoinhibitionCharaterization).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Karel Svoboda
Pew Charitable Trusts
- Nuo Li
Simons Foundation
- Nuo Li
- Karel Svoboda
Helen Hay Whitney Foundation
- Nuo Li
- Hidehiko K Inagaki
Wellcome
- Susu Chen
Robert and Janice McNair Foundation
- Nuo Li
Whitehall Foundation
- Nuo Li
Alfred P. Sloan Foundation
- Nuo Li
Kinship Foundation
- Nuo Li
National Institutes of Health (NS104781)
- Nuo Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John Huguenard, Stanford University School of Medicine, United States
Ethics
Animal experimentation: All procedures were in accordance with protocols approved by the Institutional Animal Care and Use Committees at Baylor College of Medicine (protocol AN7012), Janelia Research Campus (protocol 14-115).
Version history
- Received: May 21, 2019
- Accepted: November 16, 2019
- Accepted Manuscript published: November 18, 2019 (version 1)
- Version of Record published: December 4, 2019 (version 2)
Copyright
© 2019, Li 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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Spatiotemporal constraints on optogenetic inactivation in cortical circuits
eLife 8:e48622.
https://doi.org/10.7554/eLife.48622
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