Noninvasive optical inhibition with a red-shifted microbial rhodopsin — TEI-tagged view

Chuong, Miri, Busskamp, Matthews, Acker, Sørensen, Young, Klapoetke · 2014 · neuroscience · doi:10.1038/nn.3752 · full text at the source · TEI xml · tagged edition · index · concepts · authors
Where this record's text came from. faceted 2026-08 by reading the locally held text (xml); every evidence string verified as an exact substring of that text before merging. Claim type is method because the contribution is a reagent (a new opsin) plus its validation, not a claim about how the brain works; 'system-or-tool-building' from the supplied vocabulary fits the protein-engineering-plus-characterisation design, although the validation itself uses patch clamp, extracellular recording and Monte Carlo light-propagation simulation. The 'extends' relation names a class of prior tools rather than a single citation, but the comparison is explicit in the paper's own words and eNpHR3.0/ArchT are the named comparators in the experiments. Replication status untested: the paper reports no independent replication of Jaws. 2026-08-13, 2026-08-14 and 2026-08-15 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.
12 quotations on this page contain a reference number where the paper printed a superscript. This journal style prints citations as raised numerals — parameters12,13 — and the extraction flattened them into the line, so the sentence reads parameters 12 , 13 . The digits are citation markers and not part of what the author wrote. The quotes keep them for the same reason they keep every other extraction fault: a quote is reproduced exactly or it proves nothing.
Other fields define these differently the same word, defined another way in another discipline
principal component analysis 5 fields
Tags on this paper every tag the record carries, whether or not the words occur in the text below — a number is how many papers in the corpus carry that tag; a tag with no number is unique to this paper
Jaws cruxhalorhodopsin eNpHR3.02 ArchT2 photocurrents action spectra rebound2 transcranial transdurally optical fiber2 retinitis pigmentosa cone photoreceptors retinal ganglion hemoglobin myelination tdTomato trafficking sequences point mutations network inhibition apical dendrites2 system-or-tool-building173

Our tag layer for this paper

Cross-disciplinary analysis
content-tags & facets: phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text
phenomenonoptogenetic neural inhibition— “Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions.”
claim-typemethod— “We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula ( Halobacterium ) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers.”
method — evidence— “To enable noninvasive large-volume optogenetic inhibition, we engineered and characterized Jaws, a spectrally shifted cruxhalorhodopsin derived from the species H. salinarum (strain Shark) 17 , which mediates strong red light–driven neural inhibition.”
object of study — evidence— “A major limit to the utility of optogenetic inhibition is the addressable quantity of neural tissue. Previous optogenetic hyperpolarizing proton pumps (Arch 1 , ArchT 3 , Mac 1 ) and chloride pumps (eNpHR 4 , eNpHR3.0 (ref. 2 )) have successfully inhibited volumes of approximately a cubic millimeter, but many neuroscience questions require…
research question — evidence— “Because red light is less absorbed by hemoglobin than blue, green or yellow wavelengths, we reasoned this red-light sensitivity might render deep brain regions more accessible. We validated this through Monte Carlo modeling and direct measurement in the live mouse brain”
contribution — evidence— “Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula ( Halobacterium ) salinarum (strain Shark) and engineered to…
transferfrom tissue optics / radiative-transfer photon-transport modelling: Monte Carlo simulation of light propagation with Henyey-Greenstein and Gegenbauer-kernel anisotropic scattering phase functions, imported to predict how deep red light penetrates brain tissue and skull— “To achieve accurate simulations of light propagation close to the optical fiber, before the orientation of photon trajectories is randomized by multiple scattering events, we used an anisotropic scattering model with either Henyey-Greenstein or Gegenbauer kernel phase functions, as indicated below.”transfers[0]
transferfrom microbial biology: a rhodopsin from a halophilic archaeon, screened as a scaffold rather than studied for itself— “We therefore screened members of the cruxhalorhodopsin class in primary neuronal culture to identify molecules with both red-shifted action spectra and robust photocurrents ( Fig. 1a and Supplementary Fig. 2 ) and identified a hyperpolarizer we named Halo57, the cruxhalorhodopsin from H. salinarum (strain Shark), with less than 60% homology…transfers[1]
transferfrom ion channel biology: trafficking sequences taken from the Kir2.1 potassium channel to improve membrane delivery— “We subsequently engineered Halo57 by identifying K200R and W214F point mutations 19 , 20 ( Fig. 1b ), which significantly boosted photocurrents without altering its red action spectrum ( n = 9 or 10 cells; P = 0.02, ANOVA with Dunnett’s post hoc test), and by appending the KGC 21 or ER2 (ref. 22 ) trafficking sequences from the potassium…transfers[2]
transferfrom biomedical optics: Monte Carlo modelling of light transport, used to justify the wavelength choice before any protein was made— “Because red light is less absorbed by hemoglobin than blue, green or yellow wavelengths, we reasoned this red-light sensitivity might render deep brain regions more accessible. We validated this through Monte Carlo modeling and direct measurement in the live mouse brain”transfers[3]
mechanismHaemoglobin absorbs red light less than shorter wavelengths, so red-shifting the opsin's action spectrum lets usable light reach deeper brain tissue, which is what makes large-volume and transcranial inhibition possible.— “Because red light is less absorbed by hemoglobin than blue, green or yellow wavelengths, we reasoned this red-light sensitivity might render deep brain regions more accessible.”mechanisms[0]
mechanismA minority of recorded neurons increase firing under illumination because inhibition of upstream neurons removes their drive (network disinhibition), not because the opsin excites them.— “As others have reported, we observed a small number of neurons across multiple in vivo experiments that increased firing during optical illumination delivered either transcranially or from a 200-µm fiber, most likely as a result of network inhibition from upstream neurons”mechanisms[1]
mechanismred light reaches deeper because hemoglobin, myoglobin and lipid absorb it less than blue or yellow— “It has been previously well established that optical penetrance of mammalian tissues in the red to near-infrared (600–1,000 nm) wavelengths is better than that of bluer wavelengths, as a result of substantially less absorption from hemoglobin, myoglobin and lipid.”mechanisms[2]
mechanismthe gain came from two point mutations plus trafficking sequences borrowed from a potassium channel— “We subsequently engineered Halo57 by identifying K200R and W214F point mutations 19 , 20 ( Fig. 1b ), which significantly boosted photocurrents without altering its red action spectrum ( n = 9 or 10 cells; P = 0.02, ANOVA with Dunnett’s post hoc test), and by appending the KGC 21 or ER2 (ref. 22 ) trafficking sequences from the potassium…mechanisms[3]
mechanismrebound after illumination is attributed variously to hyperpolarisation-activated currents or to chloride accumulation shifting the reversal potential— “A rebound burst of action potentials is common after illumination of cells expressing halorhodopsins 18 , 27 – 30 or archaerhodopsins 18 , 27 , 31 , which respectively pump chloride inward and protons outward.”mechanisms[4]
mechanismramping the light down rather than switching it off halves the rebound rate and delays it fourfold— “We attempted to ameliorate this by gradually ramping down illumination over a duration of 200–1,000 ms and found that the mean rebound instantaneous firing rate dropped significantly, from 52 ± 12 Hz to 23 ± 6 Hz ( n = 16 units; P = 0.0065, paired t -test), suggesting that sculpting of light pulses may enable rebound reduction.”mechanisms[5]
mechanismthe few neurons that increased firing are attributed to inhibition of upstream neurons rather than a direct effect— “As others have reported, we observed a small number of neurons across multiple in vivo experiments that increased firing during optical illumination delivered either transcranially or from a 200-µm fiber, most likely as a result of network inhibition from upstream neurons”mechanisms[6]
builds-on the authors' earlier identification of red-shifted cruxhalorhodopsins from H. marismortui and H. vallismortis (the paper's refs 1, 18)— “In earlier work, we identified two cruxhalorhodopsins from the haloarcula H. marismortui and H.…claim_relations[0]
extends previous halorhodopsin silencers (eNpHR, eNpHR3.0)claim_relations[1]
replicates previous reports of a minority of neurons increasing firing during optogenetic inhibition (the paper's refs 3, 40, 41)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[2]
extends earlier hyperpolarising pumps, which addressed about a cubic millimetre
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[3]
contradicts the standing position that noninvasive optical inhibition was not achievable
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[4]
critiques existing inhibitors' red-light performance, at 10-30% of peak capacity
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[5]
extends eNpHR-based cone reactivation in retinitis pigmentosa models, by widening the restored spike frequency range
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[6]
confirms prior reports that a minority of neurons increase firing under optogenetic inhibition
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
claim_relations[7]
senseoptogenetic inhibition here means a light-driven ION PUMP moving chloride inward, not a channel and not a synaptic silencer - the class matters because rebound and reversal behave differently
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[0]
sensenoninvasive means no implanted optical device; the skull is intact but the virus was still injected surgically, and the paper's no-surgery scenario is explicitly future work with a transgenic line
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[1]
sensered-shifted is relative and small in absolute terms - a 14 nm shift from the standard halorhodopsin - and the practical gain comes from where that sits on the tissue absorption curve
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[2]
sensepercent inhibition here is computed over neurons SHOWING suppression, with unchanged and increased-firing units reported separately rather than folded in
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[3]
senseJaws and Jaws-ER2 are two molecules differing in trafficking sequence and are reported separately throughout
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
senses[4]
controlyellow light at 593 nm, close to the spectral peak of both opsins, used to identify which neurons express the opsin, with paired recordings of the same neurons across wavelengths — held — rules out mistaking a non-expressing neuron for an expressing one when assessing performance at the red-shifted wavelength
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
controls[0]
controlpaired recordings with an acutely inserted 200-um fiber as a positive control against transcranial illumination through the intact skull - marked PARTIAL because the paper reports in its own words that this did not settle the question — partial — rules out hyperpolarisation of superficial apical dendrites, producing somatic or downstream network inhibition, as the explanation of the noninvasive result - the paper states it CANNOT EXPLICITLY RULE OUT that possibility
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
controls[1]
auditEVIDENCE CORRECTED (RE-GROUNDED) · Jaws —is-a→ cruxhalorhodopsin — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but 'Jaws' is not named in this span, which identifies Halo57 as the cruxhalorhodopsin Jaws was engineered from; the relation holds only through that chain.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[0]
retractedEVIDENCE CORRECTED (RE-GROUNDED) · Jaws —is-a→ cruxhalorhodopsin — RE-GROUNDED. The old span described a screen of the class without naming Jaws. This sentence names both IN APPOSITION - 'a red-shifted cruxhalorhodopsin, Jaws' - which is kind-membership stated as directly as a paper ever states it.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[0]
effect directionpoint mutations —causes→ photocurrents — increases
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[1]
notepoint mutations —causes→ photocurrents — SIGN: increases, without moving the action spectrum - the two properties were separable
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[1]
effect directionJaws —causes→ rebound — increases
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[5]
holds whenJaws —causes→ rebound — relative to eNpHR3.0 and ArchT - the comparison is between opsins, not against no opsin
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[5]
noteJaws —causes→ rebound — SIGN: worse than the tools it replaces. The paper reports the axis on which its own tool loses
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[5]
weightJaws —causes→ rebound — 0.9
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[5]
outcome (stated by the tagger, no quotation)control — heldcontrols[0]
outcome (stated by the tagger, no quotation)control — partialcontrols[1]
for which uselimitation — the noninvasive results specifically: WE CANNOT EXPLICITLY RULE OUT THE POSSIBILITY THAT THE OBSERVED NONINVASIVE RESULTS WERE THE RESULT OF INDIRECT NETWORK ACTIVITY OR APICAL DENDRITIC ILLUMINATION
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[0]
for which uselimitation — any claim of depth-specific inhibition: IT IS NOT POSSIBLE TO NONINVASIVELY ILLUMINATE ONLY DEEP VOLUMES WITH OUR EXPERIMENTAL SETUP WITHOUT ALSO TARGETING SURFACE AND INTERMEDIATE LAYERS
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[1]
for which uselimitation — experimental designs built on this inhibitor: JAWS DOES YIELD POST-ILLUMINATION REBOUND, WHICH LIKELY HAS IMPLICATIONS FOR CAREFUL EXPERIMENT DESIGN
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[2]
for which uselimitation — every comparison in the paper: NO BLINDING WAS CARRIED OUT, WITH THE EXCEPTION OF COTRANSFECTED OPSIN-GFP AND TDTOMATO DATA SETS
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[3]
for which uselimitation — the same scope as items 0 and 1 - surface and intermediate layers are illuminated too, so deep effects are not isolated
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[4]
for which uselimitation — the choice between inhibitors: JAWS PRODUCED GREATER EFFECTS THAN eNpHR3.0 OR ArchT - more post-illumination rebound than the tools it replaces
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[5]
for which uselimitation — the transfer of the penetrance advantage between preparations: MYELINATION MAY STILL AFFECT OPTICAL PROPAGATION IN NEURAL TISSUE
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[6]
for which uselimitation — the generality of the engineering strategy: THE TWO HOMOLOGOUS POINT MUTATIONS DID NOT ENHANCE THE N. PHARAONIS HALORHODOPSIN - the mutations do not transfer
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[7]
for which uselimitation — the vision-restoration claim: THE RESULTANT SPIKING RATES ARE LIMITED TO LESS THAN 200 HZ, SUBSTANTIALLY LESS THAN THE FULL WILD-TYPE RANGE OF 15-450 HZ
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[8]
replicationuntested
limitationThe noninvasive results cannot be shown to be direct rather than mediated by network effects or illumination of superficial apical dendrites.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[0]
limitationTranscranial illumination cannot be confined to deep tissue with this setup.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[1]
limitationJaws still produces post-illumination rebound spiking, which constrains experimental design.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[2]
limitationExperiments were essentially unblinded and unrandomised.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[3]
limitationthe method cannot illuminate deep tissue without also illuminating everything above it, so direct deep inhibition cannot be separated from surface or dendritic effects
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[4]
limitationJaws produces MORE post-illumination rebound than the inhibitors it replaces
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[5]
limitationmyelination still affects light propagation, so red penetrance is not uniform across preparations
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[6]
limitationthe two beneficial mutations do not transfer to the halorhodopsin they were modelled on, so the engineering is scaffold-specific
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[7]
limitationeven improved, the restored retinal spiking reaches about 190 Hz against a wild-type range of 15-450 Hz
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
limitations[8]
Content tags
content-observations: finding · quantity · variable · definition · key-term — grounded in the full text
findingJaws produced significantly larger red-light photocurrents than the existing silencers eNpHR3.0 and ArchT at every light power tested in cultured neurons.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[0]
findingJaws strongly suppressed visually evoked cortical activity in vivo and restored light-driven retinal ganglion spiking in retinitis pigmentosa model mice.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[1]
findingJaws can mediate noninvasive transcranial optical inhibition of neurons deep in the brain of awake mice.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[2]
findingTranscranial red-light illumination cut firing by roughly 92% in suppressed units across motor, somatosensory, insular and piriform cortex.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[3]
findingGradually ramping the light down cut mean rebound firing from about 52 to 23 Hz, suggesting that shaping light pulses may reduce rebound.
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[4]
findingJaws gave significantly larger red-light photocurrents than eNpHR3.0 or ArchT at every power tested
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[5]
findingvisually evoked activity fell by about 86% in Jaws-expressing cortex
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[6]
findingunder red light Jaws inhibited about 89-97% while eNpHR3.0 fell to 27.5%, against 76% at its own yellow peak
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[7]
findingtranscranial illumination through intact skull suppressed firing by about 92% in neurons showing suppression, 1-3 mm deep
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[8]
findingtransdural illumination suppressed firing by about 86% in medial prefrontal cortex
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[9]
findingefficacy was similar across several millimetres of depth and across baseline firing rates
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[10]
findingin the retinitis pigmentosa model Jaws drove mean ganglion spiking of 189.5 Hz against 67.8 Hz for eNpHR, roughly tripling the bandwidth
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[11]
findingREPORTED AGAINST ITSELF: Jaws produced greater post-illumination rebound than eNpHR3.0 or ArchT
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[12]
findingramping the light down cut mean rebound firing from 52 Hz to 23 Hz
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[13]
findingthe two homologous point mutations did not enhance N. pharaonis halorhodopsin
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[14]
findingCONTROL NULL: expressing Jaws did not alter basal cell properties in culture or in slice, and its kinetics matched other inhibitors
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[15]
findingCONTROL BY DESIGN: cells were selected by an independent tdTomato marker so the photocurrent comparison could not be driven by opsin expression level
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[16]
findingDECLARED UNRESOLVABLE: surface and intermediate layers are necessarily illuminated too, so direct deep inhibition cannot be separated from dendritic or network effects
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[17]
findingthe conclusion is downgraded accordingly to highly suggestive of direct inhibition rather than demonstrated
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.findings[18]
quantity86 ± 3% — reduction of visually evoked cortical activity in Jaws-expressing visual cortex under yellow light
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[0]
quantity67.8 ± 7.0 Hz versus 189.5 ± 15.9 Hz — mean retinal ganglion cell spiking frequency driven through eNpHR versus through Jaws in blind mouse retina (a threefold bandwidth increase)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[1]
quantity14-nm — red shift of the Jaws action spectrum relative to the N. pharaonis halorhodopsin family
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[2]
quantity10–30% — fraction of peak capacity at which pre-existing optogenetic inhibitors operate under red light
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[3]
quantity1–3 mm — depth below the brain surface at which neurons were inhibited transcranially in awake mice
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[4]
quantity14 nm — spectral shift of Jaws relative to the standard halorhodopsin - small in absolute terms, decisive on the absorption curve
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[5]
quantity10-30% — fraction of peak capacity at which existing inhibitors work under red light
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[6]
quantity27.5 ± 30.3% — eNpHR3.0 red-light inhibition - note the spread exceeds the mean
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[7]
quantity189.5 vs 67.8 Hz — mean restored ganglion spiking with Jaws against eNpHR, against a wild-type range of 15-450 Hz
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[8]
quantity52 to 23 Hz — rebound firing before and after ramping the light down
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[9]
quantity1-3 mm — depth range at which transcranial inhibition was effective
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[10]
quantity13 suppressed, 9 unchanged, 3 increased — unit outcomes under transcranial illumination, reported separately
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[11]
variablelight power (independent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[1]
variabledegree of suppression (dependent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[2]
variableuninfected dentate granule cells (control)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[4]
variablephotocurrents
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[5]
variablerebound
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[6]
variabletranscranial
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[7]
definitionoptogenetic inhibition
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[0]
definitionJaws
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[1]
definitionHalo57
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[2]
definitioncruxhalorhodopsin
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[3]
definitionrebound
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[4]
definitionretinitis pigmentosa
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[5]
definitionJaws
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[6]
key-termsJaws, cruxhalorhodopsin, eNpHR3.0, ArchT, photocurrents, rebound, transcranial, optical fiber, retinitis pigmentosa, cone photoreceptors, hemoglobin, action spectra
Concepts
terms this paper carries, each with the sentence it was cut from — the layer that joins one paper to another. Terms with no quote yet are on CONCEPTS.html.
conceptJaws — not defined in this paper's own words; the engineered red-shifted chloride pump
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[0]
conceptphotocurrents — not defined in this paper's own words; light-driven current, the engineering target
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[4]
conceptrebound — not defined in this paper's own words; burst of spikes after illumination ends
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[6]
conceptpoint mutations — not defined in this paper's own words; K200R and W214F, the source of the photocurrent gain
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[17]
Statistics — cross-field join keys
field-invariant statistical terms, used in their statistical sense (gated on a number / symbol / test). A p-value or a standard deviation means the SAME thing in physics, biology, psychology and sociology — so these are the strongest cross-field join keys. Grounded verbatim.
ANOVA P as written: ANOVA followed by a Newman-Keuls multiple comparison post-test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[0]
ANOVA with Dunnett's post hoc test P
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[1]
paired t-test t as written: two-tailed paired sample t -test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[2]
Shapiro-Wilk normality test as written: tested for normality with a Shapiro-Wilk test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[3]
Kolmogorov-Smirnov test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[4]
principal component analysis as written: principal component analysis discrimination
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[5]
ANOVA with Newman-Keuls post hoc test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[6]
Kolmogorov-Smirnov test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[7]
paired t -test
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[8]
Dunnett
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[9]
Second readings
a facet read a second time, independently, from its own sentence — and whether the two readings agree
claim typemethod — a second reading reaching the same value; recorded: method
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.claim_type
methodscreening of a rhodopsin class, two point mutations and trafficking sequences, then comparison against existing inhibitors in culture, retina, slice and awake cortex — a second reading DIFFERING from the recorded value; recorded: system-or-tool-building
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.method
phenomenonlight-driven hyperpolarisation of genetically targeted neurons — a second reading DIFFERING from the recorded value; recorded: optogenetic neural inhibition
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.phenomenon

When we have changed our mind. Some entries in the table begin with a word in capitals and the reason for it. EVIDENCE CORRECTED — the finding still stands, but we had quoted the wrong sentence from the paper, and the quotation has been replaced with the right one. RETRACTED — the entry itself was wrong; it stays on the page, marked, with the reason, rather than being deleted. WITHDRAWN AND REPLACED — the entry was wrong, and a corrected version of it appears in the entries below. Each mark carries its own reason, in brackets, because the reasons differ from one entry to the next. An entry we have WITHDRAWN is removed from this page and kept in the record, with its reason. A line reading Audit and a date is a later re-reading of the entry against its whole sentence: DOUBTFUL means it was kept, and the reason says what is loose about it. Quotation marks inside the tagger's sentence. Where a tag is the tagger's own sentence, a phrase in quotation marks inside it is borrowed from the paper — the tagger's wording around it is not. The paper's own sentence is the evidence quote for that row; on this page it is withheld with the article, and the article is at its publisher. Nothing inside quotation marks anywhere on this page is ours: if it is quoted, it is the paper's. Whose words a concept carries. A concept entry records a term the paper itself uses, so the term, the sense given for it, and its evidence are the paper's own words, quoted where the paper fixes them. This is the opposite of a sense entry in the tag table, which is the tagger's sentence about how the paper uses a term. Where a concept entry could not be grounded in the paper's words, the entry says so on its own row.

Tag layer © the Meta-Tagging Project, CC BY 4.0. The paper text is © its authors/publisher and is linked, not reproduced. Excerpts shown are short quotations for identification and verification. · back to index · concepts · authors · עברית
© 2026 Shir Sivroni · ORCID 0009-0000-2597-2824