FEF inactivation with improved optogenetic methods
Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2017
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| Online Access: | http://hdl.handle.net/1721.1/108826 https://orcid.org/0000-0002-5534-6020 https://orcid.org/0000-0002-4019-7042 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 |
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| author | Acker, Leah Christine Pino, Erica N. Boyden, Edward Desimone, Robert |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science Acker, Leah Christine Pino, Erica N. Boyden, Edward Desimone, Robert |
| author_sort | Acker, Leah Christine |
| collection | MIT |
| description | Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light–shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm³ of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm²) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods). |
| first_indexed | 2024-09-23T08:41:13Z |
| format | Article |
| id | mit-1721.1/108826 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:41:13Z |
| publishDate | 2017 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1088262022-09-30T10:31:39Z FEF inactivation with improved optogenetic methods Acker, Leah Christine Pino, Erica N. Boyden, Edward Desimone, Robert Institute for Medical Engineering and Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Media Laboratory McGovern Institute for Brain Research at MIT Acker, Leah Christine Pino, Erica N. Boyden, Edward Desimone, Robert Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light–shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm³ of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm²) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods). United States. National Institutes of Health (2R44NS070453-03A1) United States. National Institutes of Health (EY017292) 2017-05-11T18:27:52Z 2017-05-11T18:27:52Z 2016-11 2016-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/108826 Acker, Leah, Erica N. Pino, Edward S. Boyden, and Robert Desimone. “FEF Inactivation with Improved Optogenetic Methods.” Proceedings of the National Academy of Sciences 113, no. 46 (November 2016): E7297–E7306. © 2016 National Academy of Sciences https://orcid.org/0000-0002-5534-6020 https://orcid.org/0000-0002-4019-7042 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 en_US http://dx.doi.org/10.1073/pnas.1610784113 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Acker, Leah Christine Pino, Erica N. Boyden, Edward Desimone, Robert FEF inactivation with improved optogenetic methods |
| title | FEF inactivation with improved optogenetic methods |
| title_full | FEF inactivation with improved optogenetic methods |
| title_fullStr | FEF inactivation with improved optogenetic methods |
| title_full_unstemmed | FEF inactivation with improved optogenetic methods |
| title_short | FEF inactivation with improved optogenetic methods |
| title_sort | fef inactivation with improved optogenetic methods |
| url | http://hdl.handle.net/1721.1/108826 https://orcid.org/0000-0002-5534-6020 https://orcid.org/0000-0002-4019-7042 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 |
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