Source 1primary paper2016Scientific Reports
Toolkit/SwiChR
SwiChR
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
PMC text for the anchor paper explicitly states that intraneural AAV6-hSyn-SwiChR-eYFP expression enabled transdermal optogenetic inhibition and sustained post-light inhibition of pain behaviors.
Usefulness & Problems
Why this is useful
SwiChR is an inhibitory opsin used in the study for optogenetic silencing of peripheral nociceptors. The summary states it enabled transdermal optogenetic inhibition and sustained post-light inhibition of pain behaviors.; optogenetic inhibition of peripheral nociceptors; sustained post-light inhibition of pain behavior; SwiChR++ is described as a bistable variant of the next-generation light-activated chloride channels developed in this study. The abstract places it among tools for reversible optogenetic inhibition across chronic and acute timescales.; reversible optogenetic inhibition; chronic and acute timescale inhibition
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SwiChR is an inhibitory opsin used in the study for optogenetic silencing of peripheral nociceptors. The summary states it enabled transdermal optogenetic inhibition and sustained post-light inhibition of pain behaviors.
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optogenetic inhibition of peripheral nociceptors
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sustained post-light inhibition of pain behavior
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SwiChR++ is described as a bistable variant of the next-generation light-activated chloride channels developed in this study. The abstract places it among tools for reversible optogenetic inhibition across chronic and acute timescales.
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reversible optogenetic inhibition
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chronic and acute timescale inhibition
Problem solved
It addresses the need for sustained optical inhibition of pain signaling in peripheral afferents.; provides inhibitory optical control of pain-related peripheral afferents; It extends the next-generation chloride-conducting channelrhodopsin design space with a bistable variant for inhibition. The paper frames these constructs as improved inhibitory optogenetic tools.; provides a bistable next-generation chloride-conducting channelrhodopsin variant for optogenetic inhibition
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It addresses the need for sustained optical inhibition of pain signaling in peripheral afferents.
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provides inhibitory optical control of pain-related peripheral afferents
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It extends the next-generation chloride-conducting channelrhodopsin design space with a bistable variant for inhibition. The paper frames these constructs as improved inhibitory optogenetic tools.
Source:
provides a bistable next-generation chloride-conducting channelrhodopsin variant for optogenetic inhibition
Problem links
provides a bistable next-generation chloride-conducting channelrhodopsin variant for optogenetic inhibition
LiteratureIt extends the next-generation chloride-conducting channelrhodopsin design space with a bistable variant for inhibition. The paper frames these constructs as improved inhibitory optogenetic tools.
Source:
It extends the next-generation chloride-conducting channelrhodopsin design space with a bistable variant for inhibition. The paper frames these constructs as improved inhibitory optogenetic tools.
provides inhibitory optical control of pain-related peripheral afferents
LiteratureIt addresses the need for sustained optical inhibition of pain signaling in peripheral afferents.
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It addresses the need for sustained optical inhibition of pain signaling in peripheral afferents.
Published Workflows
Objective: Develop and apply optogenetic and chemogenetic strategies for sustained inhibition of pain through peripheral nociceptor control.
Why it works: The study combines peripheral viral delivery of inhibitory actuators with in vivo behavioral testing, allowing direct comparison of optical and ligand-gated inhibition strategies in pain-related afferents.
optogenetic inhibition of peripheral nociceptorschemogenetic inhibition of peripheral nociceptorsAAV-mediated peripheral deliveryin vivo behavioral assay
Objective: Validate and further develop a channelrhodopsin pore selectivity model by engineering next-generation light-activated chloride channels with improved inhibitory performance.
Why it works: The abstract states that engineering was guided by a structure-informed electrostatic model for pore selectivity and by crystal structure-guided design, implying that residue-level pore features can be rationally modified to shift ion selectivity and improve inhibitory function.
ion selectivity determined by pore electrostaticselectrostatic and steric structure-function relationships of the light-gated poreinhibition mediated mainly by shunting effectsstructure-guided designcrystal structure-guided engineeringstructure-informed electrostatic modeling
Stages
- 1.Structure-informed pore selectivity modeling(library_design)
This stage exists to identify rational pore modifications expected to invert or improve ion selectivity before experimental engineering.
Selection: Development of a structure-informed electrostatic model for pore selectivity to guide residue changes in the ion conduction pathway.
- 2.Crystal structure-guided engineering of next-generation chloride channels(library_build)
This engineering stage converts model predictions into specific channel variants and seeks to overcome the small photocurrents of first-generation chloride-conducting channels.
Selection: Introduce positively charged side chains into the ion conduction pathway and remove residues hypothesized to support negatively charged binding sites for cations, then further develop next-generation variants iC++ and SwiChR++.
- 3.Functional characterization under physiological conditions(functional_characterization)
This stage tests whether engineered channels improve the electrophysiological properties that limited first-generation chloride-conducting channels.
Selection: Assess net photocurrents, reversal potential, and inhibition of spiking under physiological conditions.
- 4.In vivo and behavioral validation(in_vivo_validation)
This stage validates that the engineered channels function beyond physiological recordings and can support behavioral control in living animals.
Selection: Demonstrate strong expression in vivo and control of freely moving behavior.
Steps
- 1.Develop a structure-informed electrostatic model for pore selectivity
Guide engineering decisions about which pore residues to modify to alter ion selectivity.
The abstract states that first-generation engineering was guided in part by this model, so modeling precedes residue-level design.
- 2.Introduce positively charged pore residues and remove putative cation-binding residues
Reconfigure the ion conduction pathway to favor chloride selectivity.
These residue changes operationalize the pore selectivity model before functional testing.
- 3.Engineer next-generation variants iC++ and bistable SwiChR++engineered constructs
Further develop and validate the pore model with improved chloride-conducting channelrhodopsins.
After establishing the design logic, the campaign advances to named next-generation constructs intended to overcome first-generation limitations.
- 4.Measure photocurrent and reversal potential under physiological conditionstested constructs
Quantify whether next-generation variants improve electrophysiological performance over first-generation chloride-conducting channels.
Electrophysiological characterization is needed before in vivo use to confirm that the engineered channels have stronger and more favorable inhibitory properties.
- 5.Test inhibition of spiking relative to chloride gradients and intrinsic cell propertiestested constructs
Determine whether inhibitory function tracks expected cellular determinants.
After basic electrophysiological improvement is established, the next step is to confirm functional spike inhibition in relevant physiological contexts.
- 6.Validate in vivo expression and behavioral controlvalidated constructs
Establish practical in vivo utility and demonstrate control of freely moving behavior.
In vivo expression and behavior are downstream validations that follow successful design and physiological functional characterization.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
Computational DesignTarget processes
recombinationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: payload burdenimplementation constraint: spectral hardware requirementoperating role: regulator
The study context indicates AAV6-hSyn delivery to peripheral nociceptors and light stimulation were required. Expression was described in an AAV6-hSyn-SwiChR-eYFP format.; AAV6-hSyn delivery to peripheral afferents; optical illumination for activation; Its use requires optical control and expression of the engineered channel. The abstract does not provide further implementation details.; requires light delivery for activation
The provided evidence does not show that it avoids the need for viral transduction or light-delivery hardware.; requires viral delivery and light exposure
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2primary paper2015Proceedings of the National Academy of Sciences
Ranked Claims
The study used optogenetic and chemogenetic strategies in peripheral nociceptors to achieve sustained inhibition of pain.
The study developed optoPAIN to examine bidirectional optogenetic and chemogenetic control of pain without physically contacting the animal.
AAV6-hSyn delivery was used to express inhibitory optogenetic and chemogenetic constructs in peripheral afferents.
hM4D(Gi) expression in peripheral afferents increased mechanical and thermal thresholds in a CNO-dependent manner.
iC1C2 produced behavioral inhibition during blue-light illumination in the study.
SwiChR enabled transdermal optogenetic inhibition with sustained post-light inhibition of pain behaviors.
Next-generation chloride-conducting channelrhodopsins enabled inhibition of spiking that tracks chloride gradients and intrinsic cell properties, showed strong expression in vivo, and supported control of freely moving behavior.
inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor-based control of freely moving behavior
iC++ and SwiChR++ are next-generation light-activated chloride channels with more than 15-fold increased net photocurrents under physiological conditions and about 15 mV more negative reversal potential.
with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼ 15 mV
net photocurrent increase 15 foldreversal potential change 15 mV
The next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition.
The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition
Approval Evidence
2 sources6 linked approval claimsfirst-pass slug swichr
PMC text for the anchor paper explicitly states that intraneural AAV6-hSyn-SwiChR-eYFP expression enabled transdermal optogenetic inhibition and sustained post-light inhibition of pain behaviors.
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and a bistable variant (SwiChR++)
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applicationsupports
The study used optogenetic and chemogenetic strategies in peripheral nociceptors to achieve sustained inhibition of pain.
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deliverysupports
AAV6-hSyn delivery was used to express inhibitory optogenetic and chemogenetic constructs in peripheral afferents.
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mechanism or performancesupports
SwiChR enabled transdermal optogenetic inhibition with sustained post-light inhibition of pain behaviors.
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functional applicationsupports
Next-generation chloride-conducting channelrhodopsins enabled inhibition of spiking that tracks chloride gradients and intrinsic cell properties, showed strong expression in vivo, and supported control of freely moving behavior.
inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor-based control of freely moving behavior
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performance improvementsupports
iC++ and SwiChR++ are next-generation light-activated chloride channels with more than 15-fold increased net photocurrents under physiological conditions and about 15 mV more negative reversal potential.
with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼ 15 mV
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tool use casesupports
The next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition.
The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition
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Comparisons
Source-stated alternatives
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.; The abstract contrasts next-generation chloride-conducting channels with first-generation engineered chloride-conducting channelrhodopsins and with light-activated chloride pumps.
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The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
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The abstract contrasts next-generation chloride-conducting channels with first-generation engineered chloride-conducting channelrhodopsins and with light-activated chloride pumps.
Source-backed strengths
reported to enable sustained post-light inhibition; presented as a next-generation chloride-conducting channelrhodopsin variant
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reported to enable sustained post-light inhibition
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presented as a next-generation chloride-conducting channelrhodopsin variant
Compared with chemogenetic circuit manipulation
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to enable sustained post-light inhibition; presented as a next-generation chloride-conducting channelrhodopsin variant.
Relative tradeoffs: requires viral delivery and light exposure.
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The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Compared with hM4D(Gi)
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to enable sustained post-light inhibition; presented as a next-generation chloride-conducting channelrhodopsin variant.
Relative tradeoffs: requires viral delivery and light exposure.
Source:
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Compared with iC1C2
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to enable sustained post-light inhibition; presented as a next-generation chloride-conducting channelrhodopsin variant.
Relative tradeoffs: requires viral delivery and light exposure.
Source:
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Compared with optogenetic
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to enable sustained post-light inhibition; presented as a next-generation chloride-conducting channelrhodopsin variant.
Relative tradeoffs: requires viral delivery and light exposure.
Source:
The same paper also used iC1C2 as an inhibitory optogenetic comparator and hM4D(Gi) as a chemogenetic alternative.
Ranked Citations
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