A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman 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 towards behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driv...

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Main Authors: Xue eHan, Brian Y Chow, Huihui eZhou, Nathan C Klapoetke, Amy eChuong, Reza eRajimehr, Aimei eYang, Michael V Baratta, Jonathan eWinkle, Robert eDesimone, Edward S Boyden
Format: Article
Language:English
Published: Frontiers Media S.A. 2011-04-01
Series:Frontiers in Systems Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00018/full
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author Xue eHan
Brian Y Chow
Huihui eZhou
Nathan C Klapoetke
Amy eChuong
Reza eRajimehr
Aimei eYang
Michael V Baratta
Jonathan eWinkle
Robert eDesimone
Edward S Boyden
author_facet Xue eHan
Brian Y Chow
Huihui eZhou
Nathan C Klapoetke
Amy eChuong
Reza eRajimehr
Aimei eYang
Michael V Baratta
Jonathan eWinkle
Robert eDesimone
Edward S Boyden
author_sort Xue eHan
collection DOAJ
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 towards 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), but with a >3-fold improvement in light sensitivity over Arch, equating to >2x increase in brain tissue volume addressed by a typical single optical fiber (notably, in the typical optogenetic range of 1-10 mW/mm2). 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 function 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/sec upon illumination. A small population of neurons showed increased firing rates at long latencies following 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.
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spelling doaj.art-cb928562f61f49cc819b7f7a5e1ce68b2022-12-22T03:06:56ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372011-04-01510.3389/fnsys.2011.000188560A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortexXue eHan0Brian Y Chow1Huihui eZhou2Nathan C Klapoetke3Amy eChuong4Reza eRajimehr5Aimei eYang6Michael V Baratta7Jonathan eWinkle8Robert eDesimone9Edward S Boyden10MITMITMITMITMITMITMITMITMITMITMITTechnologies for silencing the electrical activity of genetically-targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways towards 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), but with a >3-fold improvement in light sensitivity over Arch, equating to >2x increase in brain tissue volume addressed by a typical single optical fiber (notably, in the typical optogenetic range of 1-10 mW/mm2). 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 function 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/sec upon illumination. A small population of neurons showed increased firing rates at long latencies following 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.http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00018/fullNeurophysiologyoptogeneticshalorhodopsinnon-human primateSystems neurosciencearchaerhodopsin
spellingShingle Xue eHan
Brian Y Chow
Huihui eZhou
Nathan C Klapoetke
Amy eChuong
Reza eRajimehr
Aimei eYang
Michael V Baratta
Jonathan eWinkle
Robert eDesimone
Edward S Boyden
A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
Frontiers in Systems Neuroscience
Neurophysiology
optogenetics
halorhodopsin
non-human primate
Systems neuroscience
archaerhodopsin
title A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
title_full A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
title_fullStr A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
title_full_unstemmed A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
title_short A high-light sensitivity optical neural silencer: development, and application to optogenetic control of nonhuman primate cortex
title_sort high light sensitivity optical neural silencer development and application to optogenetic control of nonhuman primate cortex
topic Neurophysiology
optogenetics
halorhodopsin
non-human primate
Systems neuroscience
archaerhodopsin
url http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00018/full
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