Heterogeneous side effects of cortical inactivation in behaving animals

Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, i...

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Autores principales:	Ariana R Andrei, Samantha Debes, Mircea Chelaru, Xiaoqin Liu, Elsa Rodarte, John L Spudich, Roger Janz, Valentin Dragoi
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	visual cortex optogenetics computation monkey electrophysiology behavior Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e181f1fee54c4be49d02779e63fda9c5
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spelling	oai:doaj.org-article:e181f1fee54c4be49d02779e63fda9c52021-11-15T07:02:27ZHeterogeneous side effects of cortical inactivation in behaving animals10.7554/eLife.664002050-084Xe66400https://doaj.org/article/e181f1fee54c4be49d02779e63fda9c52021-09-01T00:00:00Zhttps://elifesciences.org/articles/66400https://doaj.org/toc/2050-084XCortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation 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 composed 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 primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four 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. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, 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.Ariana R AndreiSamantha DebesMircea ChelaruXiaoqin LiuElsa RodarteJohn L SpudichRoger JanzValentin DragoieLife Sciences Publications Ltdarticlevisual cortexoptogeneticscomputationmonkeyelectrophysiologybehaviorMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	visual cortex optogenetics computation monkey electrophysiology behavior Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	visual cortex optogenetics computation monkey electrophysiology behavior Medicine R Science Q Biology (General) QH301-705.5 Ariana R Andrei Samantha Debes Mircea Chelaru Xiaoqin Liu Elsa Rodarte John L Spudich Roger Janz Valentin Dragoi Heterogeneous side effects of cortical inactivation in behaving animals
description	Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation 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 composed 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 primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four 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. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, 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.
format	article
author	Ariana R Andrei Samantha Debes Mircea Chelaru Xiaoqin Liu Elsa Rodarte John L Spudich Roger Janz Valentin Dragoi
author_facet	Ariana R Andrei Samantha Debes Mircea Chelaru Xiaoqin Liu Elsa Rodarte John L Spudich Roger Janz Valentin Dragoi
author_sort	Ariana R Andrei
title	Heterogeneous side effects of cortical inactivation in behaving animals
title_short	Heterogeneous side effects of cortical inactivation in behaving animals
title_full	Heterogeneous side effects of cortical inactivation in behaving animals
title_fullStr	Heterogeneous side effects of cortical inactivation in behaving animals
title_full_unstemmed	Heterogeneous side effects of cortical inactivation in behaving animals
title_sort	heterogeneous side effects of cortical inactivation in behaving animals
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/e181f1fee54c4be49d02779e63fda9c5
work_keys_str_mv	AT arianarandrei heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT samanthadebes heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT mirceachelaru heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT xiaoqinliu heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT elsarodarte heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT johnlspudich heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT rogerjanz heterogeneoussideeffectsofcorticalinactivationinbehavinganimals AT valentindragoi heterogeneoussideeffectsofcorticalinactivationinbehavinganimals
_version_	1718428526537867264

Heterogeneous side effects of cortical inactivation in behaving animals

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