Heterogeneous side-effects of cortical inactivation in behaving animals
- University of Texas, United States
- University of Texas Health Science Center at Houston, McGovern Medical School, United States
Abstract
Cortical inactivation represents a key causal manipulation that allows the study of cortical circuits and their impact on behavior. A key assumption in these studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits comprised of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate interpretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey V1 induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified 4 types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facilitation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. Importantly, these results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Furthermore, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side-effects can confound interpretation of inactivation experiments.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files are provided.
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Author details
Funding
National Institutes of Health (5U01MH109146)
- Valentin Dragoi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Texas, Houston. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Houston (Protocol number: AWC-20-0075). All surgery was performed under general anesthesia, and every effort was made to minimize suffering.
Copyright
© 2021, Andrei 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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Heterogeneous side-effects of cortical inactivation in behaving animals
eLife 10:e66400.
https://doi.org/10.7554/eLife.66400
