phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text| phenomenon | channelrhodopsin ion selectivity— “This paper tests the hypothesis that selectivity of channelrhodopsins is determined by surface potential of the pore region: Cations are conducted by a negatively charged pore, and chloride ions are conducted by a pore that has neutral and positively charged residues.” | |
| claim-type | method— “Here we describe the engineering of enhanced light-gated chloride channels (iC++ and SwiChR++) by structure-guided modification of ion selectivity, show improved efficiency for optical inhibition of neurons with these proteins, and demonstrate initial behavioral control in freely moving mammals.” | |
| method — evidence | — “In confirming this hypothesis and applying the resulting principles, we engineer improved chloride-conducting channels with higher chloride selectivity and conductivity.” | |
| object of study — evidence | — “Because optogenetic control of behavior has not yet been demonstrated with chloride channelrhodopsins, and to test further integrative ideas regarding pore function from structural considerations as shown here, we sought to design and test the next generation of enhanced chloride channels (iC++ and SwiChR++). Along the way, we provide the… | |
| research question — evidence | — “Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior.” | |
| contribution — evidence | — “Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased… | |
| transfer | from structural biology: a crystal structure and an electrostatic potential calculation, used as the design specification for a behavioural tool— “The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model” | transfers[0] |
| transfer | from synaptic physiology: shunting inhibition by GABA-A receptors, used as the model for how the engineered channel acts— “through iC++ activation will reduce excitability, just as seen with endogenous chloride-conducting channels such as GABA A receptors, providing efficient inhibition via shunting of excitatory inputs” | transfers[1] |
| mechanism | Ions are selected by electrostatic interaction with the charged residues lining the pore, so replacing glutamates with neutral/basic residues flips selectivity from cations to chloride— “The enhancements comprising iC++ support the model of channelrhodopsin selectivity ( 8 ) in which ions are selected primarily by electrostatic interactions between pore and ions.” | mechanisms[0] |
| mechanism | Protonation of basic pore residues under acidic conditions creates favourable electrostatics for chloride, which is why the earlier iC1C2 conducted chloride better at low pH— “We hypothesized that this pH dependency resulted from basic residues in the pore region of iC1C2, with higher probability of protonation under acidic conditions that established favorable electrostatic interactions for chloride ions.” | mechanisms[1] |
| mechanism | Inhibition works by shunting: opening the chloride conductance drops input resistance and shunts excitatory input, rather than by hyperpolarizing the cell— “The main mechanism of this efficient inhibition from iC++ is likely via shunting inhibition, because the V rev of iC++ lies between the V AP and V rest (revealing that the inhibition is not driven by strong hyperpolarization).” | mechanisms[2] |
| mechanism | Reduced input resistance lowers excitability in the same way endogenous GABA-A chloride channels do— “Reduction in R in through iC++ activation will reduce excitability, just as seen with endogenous chloride-conducting channels such as GABA A receptors, providing efficient inhibition via shunting of excitatory inputs ( 20 ).” | mechanisms[3] |
| mechanism | The longer arginine side chain substituted at position 134 sterically blocks channel closure, producing the dark leak current and low input resistance of the E83X mutants— “Indeed, the longer arginine side chain (compared with histidine) could, in principle, interfere with channel closure of iC1C2-E83X mutants, increasing leak currents in the dark and leading to reduced R in for these otherwise interesting E83 variants.” | mechanisms[4] |
| mechanism | ions are selected by electrostatic interaction with the pore, so replacing negatively charged residues with neutral or positive ones flips the channel from cation- to anion-conducting— “iC1C2 and iC++ are highly engineered (9 and 10 residues were replaced, respectively) variants of the cation-selective parental construct C1C2, with mutations chosen for the predicted ability to alter the electrostatic potential of the ion-conducting pore from predominantly negative to predominantly positive ( 7 , 8 , 11 ).” | mechanisms[5] |
| mechanism | inhibition works by shunting excitatory input, as endogenous chloride channels do, rather than by hyperpolarising the cell— “through iC++ activation will reduce excitability, just as seen with endogenous chloride-conducting channels such as GABA A receptors, providing efficient inhibition via shunting of excitatory inputs” | mechanisms[6] |
| mechanism | a structural argument diagnosed the leak: a longer arginine side chain where wild type has histidine could block channel closure, and reverting it restored input resistance— “Because both E83 and R134 were shown to be inner pore-gate residues in the C1C2 structure ( 7 ), we considered the possibility that a disruptive interaction had been created here by joint mutation at these two residues. Indeed, the longer arginine side chain (compared with histidine) could, in principle, interfere with channel closure of… | mechanisms[7] |
| mechanism | the pH dependence of the first-generation channel was traced to protonatable pore residues and removed by further substitution— “We hypothesized that this pH dependency resulted from basic residues in the pore region of iC1C2, with higher probability of protonation under acidic conditions that established favorable electrostatic interactions for… | mechanisms[8] |
| mechanism | channels follow the cell's own chloride gradient while pumps move ions unidirectionally regardless of it | mechanisms[9] |
| extends | iC1C2, the first-generation structure-guided chloride-conducting channelrhodopsin 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[0] |
| extends | the previously reported step-function variants SwiChR CA and SwiChR CT 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[1] |
| builds-on | the naturally anion-conducting GtACR channelrhodopsins 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] |
| builds-on | the structure-derived electrostatic model of channelrhodopsin pore selectivity 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] |
| confirms | the crystal structure-derived electrostatic model of channelrhodopsin pore selectivity 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] |
| supports | the naturally occurring GtACR chloride channels, whose pore residues match the engineered ones 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 | the first-generation iC1C2 channel, which had small photocurrents and was never tested on behaviour 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] |
| qualifies | the use of light-activated chloride pumps for 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] |
| sense | optogenetic inhibition is not one thing: a chloride CHANNEL shunts along the cell's own gradient, a chloride PUMP moves ions against it, and the two differ in efficiency, stability and dependence on the preparation 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] |
| sense | inhibitory is a property of the tool IN A PREPARATION, not of the tool - the same channel can excite where the chloride gradient runs the other way 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] |
| sense | the electrostatic pore model is treated as a predictive hypothesis, and each round of engineering is described as a test of it rather than as an application 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] |
| sense | iC++ is named for the count of charges added, so the construct name encodes the mechanistic claim 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] |
| control | matching iC++ protein expression against the parental iC1C2 construct, and comparing membrane properties of iC++-expressing cells against eYFP-only cells — held 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. — rules out that the 16-fold larger photocurrent comes from higher expression rather than from the channel itself, and that expressing the opsin alters the cell's membrane properties 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] |
| evidential status | the first-generation iC1C2 channel, which had small photocurrents and was never tested on behaviour — the paper's own words: were not 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. | claim_relations[6] |
| audit | channelrhodopsin —distinct-from→ pumps — Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span contrasts pumps with channels on light sensitivity; distinct-from is loose. 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[3] |
| differs in | channelrhodopsin —distinct-from→ pumps — THE AXIS IS LIGHT SENSITIVITY, AND A SECOND ONE IS NAMED BESIDE IT. 'the pumps, which are less light sensitive than channels and, unlike the channels, cannot be converted to a more light-sensitive bistable step-function form.' Two dimensions in one clause - how much light each needs, and whether that requirement can be engineered away. The second is the one that decides which tool a laboratory can actually use. 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[3] |
| note | channelrhodopsin —distinct-from→ pumps — differ in light sensitivity, bistability, membrane stability and whether they respect physiological gradients 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[3] |
| note | shunting —contrasted-with→ hyperpolarization — RE-GROUNDS another row of this record: the old span named ONE endpoint. 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 | control — held 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] |
| for which use | limitation — the completeness of the inhibition: nearly complete spike inhibition held even with elevated chloride, ALTHOUGH THE INHIBITION IN SUCH CASES COULD BE PARTIALLY OVERCOME WITH EXTREMELY STRONG (0.8-nA) CURRENT INJECTIONS 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 use | limitation — any reading of the paper as naming a best inhibitory tool: iC++ AND RELATED CHANNELS ... LIKE ANY REAGENT IN BIOLOGY, SHOULD BE SELECTED BASED ON SUITABILITY FOR PREPARATION AND HYPOTHESIS 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 use | limitation — the SIGN of the effect, not just its size: gradients CAN DIFFER ACROSS CELL TYPES, SUBCELLULAR REGIONS, DEVELOPMENTAL STAGES, AND PATHOLOGICAL STATES ... EVEN GIVING RISE TO EXCITATION UNDER SOME CONDITIONS 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 use | limitation — the pump comparison: THE PUMPS CAN HYPERPOLARIZE CELLS FAR BEYOND PHYSIOLOGICAL LEVELS, CAUSING UNSTABLE MEMBRANE PROPERTIES 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 use | limitation — the remedy for item 3: lowering light intensity ALSO SEVERELY REDUCES THE VOLUME OF TISSUE INHIBITED BY THE PUMPS, so the trade-off has no clean side 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] |
| duplicate of | limitation — limitations[1] 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 use | limitation — the same scope as limitations[1] - the tool is not claimed to be universally better 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 use | limitation — what the behavioural assays can resolve: EACH OPSIN WAS EQUALLY EFFECTIVE IN DRIVING REAL-TIME PLACE AVERSION, so the cellular differences do not appear at this readout 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] |
| replication | untested | |
| limitation | Spike inhibition by iC++ is not absolute: with intracellular chloride above the physiological range it can be partially overcome by very strong current injection. 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] |
| limitation | iC++ is not presented as universally superior; the choice between channel and pump depends on the preparation and hypothesis. 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] |
| limitation | because channels follow physiological gradients, which differ by cell type, subcellular region, developmental stage and pathology, the tool can even excite under some conditions 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] |
| limitation | pumps hyperpolarise far beyond physiological levels and destabilise membrane properties 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] |
| limitation | lowering pump light intensity fixes that but shrinks the inhibited tissue volume, with no clean solution 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] |
| limitation | the tool is explicitly not universally better - it must be chosen for the preparation and the hypothesis 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] |
| limitation | in both behavioural assays the three opsins performed equivalently, so the assays do not resolve the cellular differences the paper establishes 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] |
finding · quantity · variable · definition · key-term — grounded in the full text| finding | The paper tests the hypothesis that channelrhodopsin selectivity is set by the pore's surface potential: a negatively charged pore conducts cations, and a pore with neutral and positive residues conducts chloride. 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] |
| finding | Structure-guided redesign produced iC++ and the bistable SwiChR++, with more than 15-fold larger photocurrents and a reversal potential about 15 mV more negative than the previous generation. 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] |
| finding | Unlike its predecessor iC1C2, iC++ shows a reversal potential independent of the proton gradient, i.e. it does not conduct protons. 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] |
| finding | iC++ passes other halides (iodide, bromide) but excludes physiological small organic anions. 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] |
| finding | The purely model-driven engineered pore converged on the same residue solution that evolution produced in the natural anion channel GtACR2. 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] |
| finding | The chloride channel inhibited neurons far more efficiently than the chloride pump eNpHR3.0, blocking any tested input in over 90% of expressing cells. 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] |
| finding | SwiChR++ can be switched off immediately by red light, giving temporally bounded bistable control of chloride conductance and neuronal 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.findings[6] |
| finding | Under these conditions iC++, iC1C2 and eNpHR3.0 were equally effective at driving real-time place aversion. 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] |
| finding | Optogenetically silencing CREB-overexpressing amygdala neurons reduced tone-evoked freezing, while silencing an equal number of non-allocated neurons did not. 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] |
| finding | net photocurrents increased more than 15-fold under physiological conditions 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] |
| finding | effective photocurrent was more than 16 times larger than the first generation at comparable expression 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] |
| finding | the advantage over the first generation is largest for short 5 ms pulses needing over 500 pA to drive spiking 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] |
| finding | the engineered pore residues match those of a naturally occurring chloride channel discovered afterwards 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] |
| finding | Reverting one arginine to the wild-type histidine (R134H) increased input resistance and photocurrent size. 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] |
| finding | the channel inhibits spikes more efficiently than the chloride pump, through stronger shunting 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] |
| finding | all three opsins produced equivalent real-time place aversion 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] |
| finding | silencing CREB-overexpressing amygdala neurons reduced fear freezing, while silencing the same number of non-CREB neurons did not 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] |
| finding | the reduction in freezing did not differ significantly between the three opsins 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] |
| quantity | more than 16 times — increase in effective photocurrent size of iC++ over iC1C2 at comparable protein expression 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] |
| quantity | 9,500-fold (τ off,dark = 115 s ± 9) — slowing of channel closure produced by the C128A mutation, creating the bistable SwiChR++ 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] |
| quantity | 488 nm — peak activation wavelength of iC++, indicating an intact retinal-binding pocket 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] |
| quantity | near −65 mV — reversal potential of the first-generation chloride-conducting channelrhodopsins 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] |
| quantity | 9 and 10 residues — number of amino acid replacements in iC1C2 and iC++ relative to the parental cation channel C1C2 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] |
| quantity | at least seven times — efficiency advantage of the iC++ channel over the eNpHR3.0 pump in inhibiting current-driven spiking 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] |
| quantity | more than 90% — proportion of iC++-expressing cells in which light blocked every current input 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.quantities[6] |
| quantity | ∼15% — share of lateral amygdala pyramidal neurons transduced before fear conditioning in the memory-engram experiment 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] |
| quantity | more than 15-fold, and more than 16 times at matched expression — photocurrent improvement over the first generation 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] |
| quantity | reversing near -65 mV, decreased by a further about 15 mV — reversal potential of the first and second generation channels 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] |
| quantity | 9 and 10 residues replaced — how heavily engineered the two constructs are 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] |
| quantity | about 15% of lateral amygdala pyramidal neurons transduced — the engram experiment's targeting 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] |
| variable | point mutation (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[0] |
| variable | intracellular chloride concentration (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] |
| variable | external pH (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[2] |
| variable | V rev (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[3] |
| variable | neuronal input resistance (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[4] |
| variable | internal chloride concentration (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[5] |
| variable | control 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[6] |
| variable | reversal potential 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] |
| variable | photocurrent amplitude 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[8] |
| variable | avoidance of the light-paired compartment 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[9] |
| definition | channelrhodopsins 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] |
| definition | optogenetics 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] |
| definition | step-function opsin bistability 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] |
| definition | optogenetics 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] |
| definition | shunting 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[4] |
| key-terms | channelrhodopsin, optogenetics, chloride, shunting, hyperpolarization, reversal potential, photocurrent, input resistance, electrostatic, pore, crystal structure, mutation, arginine, glutamate, place-aversion, engram, amygdala, CREB, freezing, bistable |
| ANOVA (two-way repeated measures) F | as written: two-way repeated-measures ANOVA, main effect of light power, F 2, 18 = 64.529 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] |
| post hoc multiple comparison test (Holm-Sidak) | as written: Holm–Sidak post hoc tests 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] |
| interaction effect in factorial ANOVA F 6,52 | as written: light (on, off) × virus ANOVA yielded a significant interaction 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] |
| standard error of the mean SEM | as written: 12.1 ms ± 0.4 SEM 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] |
| two-way repeated-measures ANOVA with Holm-Sidak post hoc | 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] |
| light by virus interaction ANOVA | 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] |
| claim type | mechanism — a second reading DIFFERING from the recorded 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 |
| method | structure-guided point mutation with whole-cell recording in cultured neurons, then viral expression and behavioural testing in freely moving mice — 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 |
| phenomenon | ion selectivity in a light-gated channel pore — a second reading DIFFERING from the recorded value; recorded: channelrhodopsin ion selectivity 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.
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