Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2
Channelrhodopsin-2 (ChR2) has quickly gained popularity as a powerful tool for eliciting genetically targeted neuronal activation. However, little has been reported on the response kinetics of optogenetic stimulation across different neuronal subtypes. With excess stimulation, neurons can be driven...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01481 |
| _version_ | 1828166327232102400 |
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| author | Alexander M Herman Longwen Huang Dona K Murphey Isabella Garcia Benjamin R Arenkiel |
| author_facet | Alexander M Herman Longwen Huang Dona K Murphey Isabella Garcia Benjamin R Arenkiel |
| author_sort | Alexander M Herman |
| collection | DOAJ |
| description | Channelrhodopsin-2 (ChR2) has quickly gained popularity as a powerful tool for eliciting genetically targeted neuronal activation. However, little has been reported on the response kinetics of optogenetic stimulation across different neuronal subtypes. With excess stimulation, neurons can be driven into depolarization block, a state where they cease to fire action potentials. Herein, we demonstrate that light-induced depolarization block in neurons expressing ChR2 poses experimental challenges for stable activation of specific cell types and may confound interpretation of experiments when ‘activated’ neurons are in fact being functionally silenced. We show both ex vivo and in vivo that certain neuronal subtypes targeted for ChR2 expression become increasingly susceptible to depolarization block as the duration of light pulses are increased. We find that interneuron populations have a greater susceptibility to this effect than principal excitatory neurons, which are more resistant to light-induced depolarization block. Our results highlight the need to empirically determine the photo-response properties of targeted neurons when using ChR2, particularly in studies designed to elicit complex circuit responses in vivo where neuronal activity will not be recorded simultaneous to light stimulation. |
| first_indexed | 2024-04-12T01:59:31Z |
| format | Article |
| id | doaj.art-ac8d55a6f0774af49a31ff40673006fc |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:59:31Z |
| publishDate | 2014-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ac8d55a6f0774af49a31ff40673006fc2022-12-22T03:52:43ZengeLife Sciences Publications LtdeLife2050-084X2014-01-01310.7554/eLife.01481Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2Alexander M Herman0Longwen Huang1Dona K Murphey2Isabella Garcia3Benjamin R Arenkiel4Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United States; Medical Scientist Training Program, Baylor College of Medicine, Houston, United StatesProgram in Developmental Biology, Baylor College of Medicine, Houston, United States; Department of Neuroscience, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesChannelrhodopsin-2 (ChR2) has quickly gained popularity as a powerful tool for eliciting genetically targeted neuronal activation. However, little has been reported on the response kinetics of optogenetic stimulation across different neuronal subtypes. With excess stimulation, neurons can be driven into depolarization block, a state where they cease to fire action potentials. Herein, we demonstrate that light-induced depolarization block in neurons expressing ChR2 poses experimental challenges for stable activation of specific cell types and may confound interpretation of experiments when ‘activated’ neurons are in fact being functionally silenced. We show both ex vivo and in vivo that certain neuronal subtypes targeted for ChR2 expression become increasingly susceptible to depolarization block as the duration of light pulses are increased. We find that interneuron populations have a greater susceptibility to this effect than principal excitatory neurons, which are more resistant to light-induced depolarization block. Our results highlight the need to empirically determine the photo-response properties of targeted neurons when using ChR2, particularly in studies designed to elicit complex circuit responses in vivo where neuronal activity will not be recorded simultaneous to light stimulation.https://elifesciences.org/articles/01481optogeneticsaction potentialin vivochannelrhodopsinsilencing |
| spellingShingle | Alexander M Herman Longwen Huang Dona K Murphey Isabella Garcia Benjamin R Arenkiel Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 eLife optogenetics action potential in vivo channelrhodopsin silencing |
| title | Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 |
| title_full | Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 |
| title_fullStr | Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 |
| title_full_unstemmed | Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 |
| title_short | Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2 |
| title_sort | cell type specific and time dependent light exposure contribute to silencing in neurons expressing channelrhodopsin 2 |
| topic | optogenetics action potential in vivo channelrhodopsin silencing |
| url | https://elifesciences.org/articles/01481 |
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