A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex
Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven...
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| Format: | Article |
| Language: | en_US |
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Frontiers Research Foundation
2012
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| Online Access: | http://hdl.handle.net/1721.1/70022 https://orcid.org/0000-0002-8860-5914 https://orcid.org/0000-0003-3466-8706 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 |
| _version_ | 1826203948471549952 |
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| author | Han, Xue Chow, Brian Y. Zhou, Huihui Klapoetke, Nathan Cao Chuong, Amy S. Rajimehr, Reza Yang, Aimei Baratta, Michael V. Winkle, Jonathan Andrew Desimone, Robert Boyden, Edward Stuart |
| author2 | Massachusetts Institute of Technology. Synthetic Neurobiology Group |
| author_facet | Massachusetts Institute of Technology. Synthetic Neurobiology Group Han, Xue Chow, Brian Y. Zhou, Huihui Klapoetke, Nathan Cao Chuong, Amy S. Rajimehr, Reza Yang, Aimei Baratta, Michael V. Winkle, Jonathan Andrew Desimone, Robert Boyden, Edward Stuart |
| author_sort | Han, Xue |
| collection | MIT |
| description | Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications. |
| first_indexed | 2024-09-23T12:45:58Z |
| format | Article |
| id | mit-1721.1/70022 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:45:58Z |
| publishDate | 2012 |
| publisher | Frontiers Research Foundation |
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| spelling | mit-1721.1/700222022-09-28T09:54:35Z A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex Han, Xue Chow, Brian Y. Zhou, Huihui Klapoetke, Nathan Cao Chuong, Amy S. Rajimehr, Reza Yang, Aimei Baratta, Michael V. Winkle, Jonathan Andrew Desimone, Robert Boyden, Edward Stuart Massachusetts Institute of Technology. Synthetic Neurobiology Group Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Media Laboratory McGovern Institute for Brain Research at MIT Program in Media Arts and Sciences (Massachusetts Institute of Technology) Desimone, Robert Han, Xue Chow, Brian Y. Zhou, Huihui Klapoetke, Nathan Cao Chuong, Amy S. Rajimehr, Reza Yang, Aimei Baratta, Michael V. Winkle, Jonathan Andrew Desimone, Robert Boyden, Edward Stuart Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications. Helen Hay Whitney Foundation National Institutes of Health (U.S.) (NIH K99MH085944) McGovern Institute Neurotechnology (MINT) Program National Institutes of Health (U.S.) (Director’s New Innovator Award 1DP2OD002002, 1R01DA029639, 1R43NS070453, 1RC2DE020919, 1R01NS067199) National Science Foundation (U.S.) (NSF (EFRI 0835878)) National Science Foundation (U.S.) (DMS 0848804) United States. Dept. of Defense Brain & Behavior Research Foundation Alfred P. Sloan Foundation Dr. Gerald Burnett and Marjorie Burnett SFN Research Award for Innovation in Neuroscience Massachusetts Institute of Technology. Media Laboratory McGovern Institute for Brain Research at MIT Benesse Foundation Massachusetts Institute of Technology (Neurotechnology Fund) Wallace H. Coulter Foundation 2012-04-13T16:59:59Z 2012-04-13T16:59:59Z 2011-04 Article http://purl.org/eprint/type/JournalArticle 1662-5137 http://hdl.handle.net/1721.1/70022 Han, Xue et al. “A High-Light Sensitivity Optical Neural Silencer: Development and Application to Optogenetic Control of Non-Human Primate Cortex.” Frontiers in Systems Neuroscience 5 (2011): 1-8. https://orcid.org/0000-0002-8860-5914 https://orcid.org/0000-0003-3466-8706 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 en_US http://dx.doi.org/10.3389/fnsys.2011.00018 Frontiers in Systems Neuroscience 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 Frontiers Research Foundation Frontiers |
| spellingShingle | Han, Xue Chow, Brian Y. Zhou, Huihui Klapoetke, Nathan Cao Chuong, Amy S. Rajimehr, Reza Yang, Aimei Baratta, Michael V. Winkle, Jonathan Andrew Desimone, Robert Boyden, Edward Stuart A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title | A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title_full | A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title_fullStr | A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title_full_unstemmed | A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title_short | A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex |
| title_sort | high light sensitivity optical neural silencer development and application to optogenetic control of non human primate cortex |
| url | http://hdl.handle.net/1721.1/70022 https://orcid.org/0000-0002-8860-5914 https://orcid.org/0000-0003-3466-8706 https://orcid.org/0000-0002-0419-3351 https://orcid.org/0000-0002-5938-4227 |
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