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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66400 |
| _version_ | 1811227380075724800 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T09:41:35Z |
| format | Article |
| id | doaj.art-e181f1fee54c4be49d02779e63fda9c5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:41:35Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e181f1fee54c4be49d02779e63fda9c52022-12-22T03:38:04ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.66400Heterogeneous side effects of cortical inactivation in behaving animalsAriana R Andrei0https://orcid.org/0000-0003-2152-2580Samantha Debes1Mircea Chelaru2Xiaoqin Liu3Elsa Rodarte4John L Spudich5https://orcid.org/0000-0003-4167-8590Roger Janz6Valentin Dragoi7https://orcid.org/0000-0002-9526-0926Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurology, McGovern Medical School, University of Texas, Houston, United StatesCenter for Membrane Biology, Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesDepartment of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United StatesCortical 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.https://elifesciences.org/articles/66400visual cortexoptogeneticscomputationmonkeyelectrophysiologybehavior |
| spellingShingle | 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 eLife visual cortex optogenetics computation monkey electrophysiology behavior |
| title | 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_short | Heterogeneous side effects of cortical inactivation in behaving animals |
| title_sort | heterogeneous side effects of cortical inactivation in behaving animals |
| topic | visual cortex optogenetics computation monkey electrophysiology behavior |
| url | https://elifesciences.org/articles/66400 |
| 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 |