Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution.
The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a li...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-03-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0000299 |
| _version_ | 1818586179490021376 |
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| author | Xue Han Edward S Boyden |
| author_facet | Xue Han Edward S Boyden |
| author_sort | Xue Han |
| collection | DOAJ |
| description | The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells. |
| first_indexed | 2024-12-16T08:48:51Z |
| format | Article |
| id | doaj.art-3cfe44b40b7344ffa4afb28d440ffb56 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:48:51Z |
| publishDate | 2007-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3cfe44b40b7344ffa4afb28d440ffb562022-12-21T22:37:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-03-0123e29910.1371/journal.pone.0000299Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution.Xue HanEdward S BoydenThe quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells.https://doi.org/10.1371/journal.pone.0000299 |
| spellingShingle | Xue Han Edward S Boyden Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS ONE |
| title | Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. |
| title_full | Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. |
| title_fullStr | Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. |
| title_full_unstemmed | Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. |
| title_short | Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. |
| title_sort | multiple color optical activation silencing and desynchronization of neural activity with single spike temporal resolution |
| url | https://doi.org/10.1371/journal.pone.0000299 |
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