Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals Stark Koos Buzsáki

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Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals 2012 Journal of Neurophysiology 10.1152/jn.00153.2012 Stark2012-diode-probes-for-spatiotemporal-optical-cont Stark2012-diode-probes-for-spatiotemporal-optical-cont.txt, the project's staged copy 42e122ebbb581aa491b4fd714f5d10131e4bae3e not-redistributable neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them an instrument: independent optical control of many sites in the brain of a freely moving animal, with the stimulated neurons recorded at the same time Quotation withheld because this record is not cleared for redistribution. how to stimulate exactly the neurons being monitored, when electrodes hear only 60 μm and every existing light source reaches far further than that Quotation withheld because this record is not cleared for redistribution. a diode-fiber assembly light enough to put one on every shank - local photostimulation and recording of the same cells, without light artifacts, spike superposition or a fiber tether Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. multisite optogenetic control of neurons in freely moving animals Quotation withheld because this record is not cleared for redistribution. system-or-tool-building system-or-tool-building Quotation withheld because this record is not cleared for redistribution. mechanisms Putting the fiber tip within tens of μm of the recording sites means very little light is needed, which in turn removes the need for high currents and lets the device avoid heat sinks, optical artifacts and spike superposition while confining the effect to the monitored neurons Quotation withheld because this record is not cleared for redistribution. mechanisms An index-matched glue at the diode–fiber interface cuts Fresnel reflection losses and widens the fiber's acceptance angle for skew rays, which is why coupled power doubles Quotation withheld because this record is not cleared for redistribution. mechanisms Red-light-driven halorhodopsin hyperpolarisation of the membrane delays the ChR2-evoked spike, which is why latencies lengthen when activation and silencing are applied together Quotation withheld because this record is not cleared for redistribution. mechanisms The unusually high fraction of responsive units follows from the high AAV transduction rate combined with the very short distance between fiber tip and recording sites Quotation withheld because this record is not cleared for redistribution. the light is weak and the fiber tip is close, so the illuminated volume is about 0.001 mm 3 - the cells the light reaches are the cells the shank can hear Quotation withheld because this record is not cleared for redistribution. a drop of index-matching glue at the diode-fiber interface, which cuts the reflective losses at each interface from 8% to under 1% Quotation withheld because this record is not cleared for redistribution. and the same glue admits skew rays from all directions, which is where the doubling in coupling efficiency actually comes from Quotation withheld because this record is not cleared for redistribution. with the light path perpendicular to the recording sites and the power several orders of magnitude below laser stimulation, so there are no local field potential artifacts to interpret Quotation withheld because this record is not cleared for redistribution. The spatial confinement of the photostimulus is itself a drawback for experiments that need a whole structure controlled synchronously. what this limits: the confinement that is the method's selling point: FOR SOME APPLICATIONS, THE USE OF SPATIALLY RESTRICTED PHOTOSTIMULATION FOR LOCALIZED NEURONAL CONTROL IS ACTUALLY A LIMITATION - an advantage for one use and a defect for another Quotation withheld because this record is not cleared for redistribution. The 1/d scattering model used to estimate light intensity overestimates power beyond 1 mm from the fiber tip. what this limits: every light-intensity figure beyond 1 mm from the tip: THE MODEL CONSISTENTLY OVERESTIMATED POWER AT DISTANCES >1 MM, while POWER AT SHORTER DISTANCES WAS WELL-APPROXIMATED Quotation withheld because this record is not cleared for redistribution. The fluorescein-bath measurement of the light cone is only an approximation of the real geometric light distribution in brain tissue. what this limits: the measured light cone: THIS IS ONLY A PROXY TO THE REAL GEOMETRIC DISTRIBUTION OF LIGHT IN THE BRAIN SINCE SCATTERING MAY CONTRIBUTE ... ESPECIALLY AT SHORT WAVELENGTHS Quotation withheld because this record is not cleared for redistribution. THE PAPER'S HEADLINE ADVANTAGE, RE-TAGGED AS A LIMITATION: spatially restricted photostimulation IS ACTUALLY A LIMITATION for experiments requiring synchronous control of an entire structure what this limits: experiments requiring synchronous control of an entire structure, where the spatial extent should be two to three orders of magnitude higher than the 0.001 mm 3 a shank can monitor Quotation withheld because this record is not cleared for redistribution. the scattering model consistently overestimated power beyond 1 mm, and scattering ran 5 to 10% higher in tissue that was not fresh what this limits: the same scope as limitations[1], plus the tissue caveat: SCATTERING WAS SLIGHTLY HIGHER (5-10%) IN NONFRESH TISSUE Quotation withheld because this record is not cleared for redistribution. the fluorescein image is declared A PROXY ONLY for the real geometric distribution of light in the brain, since scattering contributes to it at short wavelengths duplicate of: limitations[2] · what this limits: the same scope as limitations[2] - the fluorescein image stands in for the real distribution Quotation withheld because this record is not cleared for redistribution. the high fraction of light-modulated units MAY BE DUE TO transduction rates and the proximity of the fiber tip rather than to anything general what this limits: the fraction of units reported as light-modulated: it MAY BE DUE TO THE HIGH ChR2 TRANSDUCTION RATES ... AND THE PROXIMITY OF THE FIBER TIP TO THE RECORDING SITES Quotation withheld because this record is not cleared for redistribution. and the count of illuminated cells rests on an assumed neuronal density and IGNORES SHADOWING by the probe shank what this limits: the count of illuminated cells: THE ESTIMATION ... ASSUMES NEURONAL DENSITY OF 20,000 CELLS/MM3 AND IGNORES SHADOWING BY THE PROBE SHANK Quotation withheld because this record is not cleared for redistribution. with the number of fibers a freely moving animal can be tethered to limited to one or two, which RESTRICTED the range of scientific questions that could be addressed what this limits: what could be asked before this method, not only what could be measured: SINCE THE NUMBER OF FIBERS A FREELY MOVING ANIMAL CAN BE TETHERED TO IS LIMITED (1-2 FOR SMALL RODENTS), THE RANGE OF SCIENTIFIC QUESTIONS THAT COULD BE ADDRESSED WAS RESTRICTED Quotation withheld because this record is not cleared for redistribution. for a uniform planar (Lambertian) light source and a straight cleaved optical fiber having a numerical aperture, the maximum coupling efficiency of Hudson 1974 Quotation withheld because this record is not cleared for redistribution. reflective losses, quantified by the Fresnel equations at each interface, and skew rays - two factors with opposing practical implications, both ignored in the standard coupling formula Quotation withheld because this record is not cleared for redistribution. a 1/d scattering model fitted to power measured through a block of brain, giving a scattering coefficient per wavelength Quotation withheld because this record is not cleared for redistribution. red laser diodes driven by similar currents, yielding light at the fiber tip that subtended a similar illuminated volume of brain tissue Quotation withheld because this record is not cleared for redistribution. waveguides embedded in the probe shank, named as the route to scaling the number of sources Quotation withheld because this record is not cleared for redistribution. closed-loop triggering - the recorded signal decides when the stimulus happens Quotation withheld because this record is not cleared for redistribution. spike waveforms during light compared with waveforms during spontaneous activity eliminates: the light distorting or superimposing the spikes it evokes - median waveform consistencies 0.977 against 0.983, U test P = 0.19 · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. units recorded on the shanks that were NOT illuminated, 200 μm and further away eliminates: the effect spreading beyond the illuminated shank - 52% modulated on the lit shank against 6.8% nearby, at chance level by an exact binomial test · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. the same cross-correlation histograms computed over a duration-matched baseline period before any stimulation eliminates: the correlations being native rather than induced - the baseline histograms were nearly flat WITH AN EXCEPTION, a 1-ms lag between the units on shanks 4 and 3 · outcome (stated by the tagger, no quotation): partial Quotation withheld because this record is not cleared for redistribution. the wideband traces inspected for photoelectrical artifacts at the light powers actually used eliminates: light artifacts masquerading as physiology - the weak stimulus produced no LFP artifacts, unlike powers three orders of magnitude higher · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. the scattering fit repeated across tip morphology, source power and brain region eliminates: the attenuation constant depending on how it was measured - it did not, EXCEPT that scattering was 5 to 10% higher in nonfresh tissue and the model overestimates beyond 1 mm · outcome (stated by the tagger, no quotation): partial Quotation withheld because this record is not cleared for redistribution. THE PAPER'S HEADLINE ADVANTAGE, RE-TAGGED AS A LIMITATION BY ITS OWN AUTHORS: for some applications the use of SPATIALLY RESTRICTED PHOTOSTIMULATION for localized neuronal control IS ACTUALLY A LIMITATION - where synchronous control of an entire structure is wanted, the spatial extent should be two to three ORDERS OF MAGNITUDE HIGHER than the 0.001 mm 3 that can be monitored Quotation withheld because this record is not cleared for redistribution. and the resolution is not a better setting but a different question - THE SPECIFIC LIGHT SOURCES AND FIBERS SHOULD BE TAILORED TO THE SCIENTIFIC QUESTION AT HAND Quotation withheld because this record is not cleared for redistribution. ONE INTERVENTION, TWO COMPONENTS, OPPOSITE SIGNS: the index-matching glue reduces reflective losses considerably, to under 1%, BUT AT A COST OF REDUCING the effective acceptance angle of the fiber BY 41% Quotation withheld because this record is not cleared for redistribution. the same glue on the other component: its effect on the SKEW RAYS acceptance angle is DIAMETRICALLY OPPOSITE from its effect on the meridional one, enabling acceptance from all directions and A TWOFOLD INCREASE in coupling efficiency - the net sign is empirical, not derivable Quotation withheld because this record is not cleared for redistribution. with the two ignored factors named as ignored: TWO FACTORS, WHICH HAVE OPPOSING PRACTICAL IMPLICATIONS, WERE IGNORED IN THE FOREGOING - reflective losses, and skew rays Quotation withheld because this record is not cleared for redistribution. A MEASURED CONSTANT THAT DISAGREES WITH THE PUBLISHED ONE, AND THE DISAGREEMENT DECLARED NOT TO MATTER: blue-light scattering 7.18 against a previously reported 10.3 for rat brain, explained by the slightly different testing conditions - and IN ANY EVENT estimates were SIMILAR REGARDLESS OF THE PRECISE NUMBER USED Quotation withheld because this record is not cleared for redistribution. the model's own failure stated with its range: it CONSISTENTLY OVERESTIMATED power beyond 1 mm while fitting well below it, and scattering was 5 to 10% higher in nonfresh tissue Quotation withheld because this record is not cleared for redistribution. and the empirical map declared a proxy: THIS IS ONLY A PROXY to the real geometric distribution of light in the brain, since scattering may contribute, ESPECIALLY AT SHORT WAVELENGTHS Quotation withheld because this record is not cleared for redistribution. WHY THE LIGHT HAS TO BE WEAK AND CLOSE: electrodes can only disambiguate spikes of neurons up to 60 μm away, so stimulating from the surface or from a fiber a few hundred μm off INEVITABLY ACTIVATES MANY MORE UNMONITORED NEURONS THAN ARE BEING MONITORED, MAKING THE SEPARATION BETWEEN DIRECT AND POPULATION-MEDIATED EFFECTS IMPOSSIBLE Quotation withheld because this record is not cleared for redistribution. and strong light of ANY wavelength carries energy dissipated as HEAT, which has a MIXED DE-/HYPERPOLARIZING effect - a confound that does not depend on the opsin at all Quotation withheld because this record is not cleared for redistribution. THE SAME LIGHT, THE OPPOSITE SIGN, DECIDED BY THE PROMOTER: identical parameters in CA1 give robust spiking of pyramidal cells in CaMKII::ChR2 mice, and in PV::ChR2 mice spiking of interneurons FOLLOWED BY SILENCING of the nearby pyramidal cells Quotation withheld because this record is not cleared for redistribution. A 25% CHANGE IN DOSE FLIPS THE OUTCOME: 70% of the 0.35 mW/mm 2 blue pulses overcame the red-light hyperpolarization but ONLY 10% of the 0.28 mW/mm 2 pulses did - the same two opsins, the same cells, and a sharp threshold between activation and silencing Quotation withheld because this record is not cleared for redistribution. a statistical definition rescued by the data's own shape: the definition of light-modulated spiking WAS STATISTICAL, but the modulation indices exhibited a BIMODAL distribution, 0.045 against 0.76 Quotation withheld because this record is not cleared for redistribution. with the fraction itself hedged - the relatively high fraction MAY BE DUE TO high transduction rates and the proximity of the fiber tip Quotation withheld because this record is not cleared for redistribution. THE UNIT IS DEFINED BY THREE NUMBERED GATES BEFORE ANY RESULT IS COMPUTED: peak-to-peak amplitude above 50 microvolts, L ratio below 0.05, and a clear refractory period - and then a fourth for the statistics, at least 100 spikes above 0.01 spikes/s Quotation withheld because this record is not cleared for redistribution. an idealisation declared inside a figure legend: the estimate ASSUMES neuronal density of 20,000 cells/mm 3 and IGNORES SHADOWING by the probe shank Quotation withheld because this record is not cleared for redistribution. the temporal resolution stated as three numbers that mean different things - center-of-mass 12 ms, latency 5.5 ms, and precision, the across-trial SD, 2 ms Quotation withheld because this record is not cleared for redistribution. AND THE INSTRUMENT'S PURPOSE IS A DEBATE: spatiotemporally sequenced activity at different timescales COULD ADDRESS THE DEBATE ON RATE VS. TEMPORAL CODING - the same debate Levi2022 would later call rooted in definitions Quotation withheld because this record is not cleared for redistribution. and the synthetic pattern is taken up by the native one: units driven by nonperiodic photostimuli exhibited PHASE PRECESSION, indicating that NATIVE NETWORK DYNAMICS CAN INCORPORATE SYNTHETIC PATTERNS OF ACTIVITY Quotation withheld because this record is not cleared for redistribution. with the constraint that motivated the whole device stated as a number: the number of fibers a freely moving animal can be tethered to is ONE TO TWO for small rodents, and that RESTRICTED THE RANGE OF SCIENTIFIC QUESTIONS THAT COULD BE ADDRESSED Quotation withheld because this record is not cleared for redistribution. claim_type: method a second reading reaching the same value. Recorded: method — note: a second reading reaching the same value from a different sentence. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: couple a miniature diode to a small-core fiber etched to a point, glue it 50 μm above the top recording site, and drive each diode from its own precision current channel a second reading DIFFERING from the recorded value. Recorded: system-or-tool-building — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: light-evoked spiking in intact tissue, and how far in space and time the evoked spikes stay where they were aimed a second reading DIFFERING from the recorded value. Recorded: multisite optogenetic control of neurons in freely moving animals — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. extends → Royer et al. 2010 (small-core fibers coupled to DPSS lasers at low power) Quotation withheld because this record is not cleared for redistribution. contradicts → Aravanis et al. 2007 (published blue-light scattering coefficient for rat brain) Quotation withheld because this record is not cleared for redistribution. builds-on → Fujisawa et al. 2008 (probe implantation methods) Quotation withheld because this record is not cleared for redistribution. contradicts → the previously reported blue-light scattering coefficient for rat brain, 10.3, against 7.18 measured here differs in: light was shined through brain slices in the previous measurements, which causes reflective losses Quotation withheld because this record is not cleared for redistribution. critiques → stimulation from the brain surface or from large fibers hundreds of μm away, which activates far more neurons than are monitored differs in: THE AXIS IS THE MISMATCH BETWEEN THE RECORDED AND THE ILLUMINATED VOLUME. 'such electrodes can only record and disambiguate spikes of nearby (UP TO 60 UM) NEURONS, [so] stimulation of continuously monitored cells requires placing the light source very close to the recording site.' The recording radius is given as a number and the stimulated volume is larger - so a causal claim from optogenetics rests on cells that were driven and never observed. Quotation withheld because this record is not cleared for redistribution. critiques → large-core fibers driven by strong light sources, which add heat, photoelectrical artifacts and synchronous activation differs in: THE AXIS IS HEAT AS A CONFOUND OF THE LIGHT ITSELF. 'Quotation withheld.' The control for an optogenetic manipulation is light, and light is not inert - the confound is a property of the energy delivered, so it is present in every experiment of this kind at sufficient power. Quotation withheld because this record is not cleared for redistribution. distinguishes-from → small-core fibers coupled to lasers at low power, which solved the artifact problem but not the tether limit of one to two fibers differs in: THE AXIS IS THE TETHER LIMIT, GIVEN AS A NUMBER. 'THESE ISSUES WERE PREVIOUSLY ADDRESSED IN PART BY COUPLING SMALL-CORE FIBERS TO DPSS LASERS DRIVEN AT LOW POWER, BUT SINCE THE NUMBER OF FIBERS A freely moving animal can be tethered to is limited (1-2 FOR SMALL RODENTS), the range of scientific questions that could be addressed was restricted.' The earlier solution is credited with fixing the artifact and charged with a different limit - so the two are not better and worse, they fail at different points. Quotation withheld because this record is not cleared for redistribution. supports → coincidence between the illuminated volume and the volume a silicon probe shank can monitor, as the condition for separating direct from population-mediated effects Quotation withheld because this record is not cleared for redistribution. predicts → that MEMS integration of diode dies with waveguides in the shank will scale up the number of light sources Quotation withheld because this record is not cleared for redistribution. qualifies → its own central advantage, which is a limitation whenever the question needs an entire structure driven at once differs in: THE AXIS IS WHETHER THE QUESTION NEEDS A WHOLE STRUCTURE DRIVEN AT ONCE. 'Quotation withheld.' The paper's own headline advantage is a defect for a class of question, said by the authors - so 'higher spatial precision' is not an improvement, it is a trade whose sign depends on the experiment. Quotation withheld because this record is not cleared for redistribution. photostimulation —is-a→ limitation photostimulation limitation strength of the relation: 1 · note: THE HEADLINE ADVANTAGE RE-TAGGED AS A LIMITATION BY ITS OWN AUTHORS - spatially restricted photostimulation IS ACTUALLY A LIMITATION for experiments requiring synchronous control of an entire structure Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span calls spatially restricted photostimulation a limitation for some uses; is-a is loose. Quotation withheld because this record is not cleared for redistribution. fiber —causes→ volume fiber volume strength of the relation: 1 · note: and the choice is not a better setting but a different question - THE SPECIFIC LIGHT SOURCES AND FIBERS SHOULD BE TAILORED TO THE SCIENTIFIC QUESTION AT HAND Audit 2026-09-28: DOUBTFUL - read against its span and kept, but multiple fibers can illuminate a large volume; causes is loose. Quotation withheld because this record is not cleared for redistribution. reflective losses —causes→ coupling reflective losses coupling strength of the relation: 1 · note: TWO FACTORS, WHICH HAVE OPPOSING PRACTICAL IMPLICATIONS, WERE IGNORED IN THE FOREGOING - reflective losses, quantified by the Fresnel equations at 8%, and skew rays Audit 2026-09-28: DOUBTFUL - read against its span and kept, but reflective losses and skew rays have opposing implications for coupling; causes is loose and unsigned. Quotation withheld because this record is not cleared for redistribution. skew rays —causes→ coupling skew rays coupling strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but reflective losses and skew rays have opposing implications for coupling; causes is loose and unsigned. Quotation withheld because this record is not cleared for redistribution. index —causes→ reflective losses index reflective losses strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but a matched coupling index reduces reflective losses; the edge carries no direction. Quotation withheld because this record is not cleared for redistribution. index —causes→ acceptance angle index acceptance angle strength of the relation: 1 · note: ONE INTERVENTION, OPPOSITE SIGNS - the glue reduces reflective losses to under 1% BUT AT A COST OF REDUCING the effective acceptance angle BY 41% Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span relates the coupling index to the acceptance angle; causes is loose. Quotation withheld because this record is not cleared for redistribution. skew rays —contrasted-with→ meridional skew rays meridional strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but skew rays versus meridional rays; contrasted-with is implied. Quotation withheld because this record is not cleared for redistribution. light —causes→ artifact light artifact strength of the relation: 1 · note: the high intensity used for deep neurons may generate superposition of multiple spike waveforms and CONSIDERABLE LIGHT ARTIFACTS Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span discusses artifacts from light near electrodes; causes is loose. Quotation withheld because this record is not cleared for redistribution. light —causes→ heat light heat strength of the relation: 1 · note: strong light OF ANY WAVELENGTH carries considerable energy dissipated as heat - a confound that does not depend on the opsin Quotation withheld because this record is not cleared for redistribution. heat —causes→ neuron heat neuron strength of the relation: 1 · note: local heating has a MIXED DE-/HYPERPOLARIZING effect, which may confound and/or limit the effect of the optogenetic manipulation itself Audit 2026-09-28: DOUBTFUL - read against its span and kept, but local heating can affect neurons; causes is loose. Quotation withheld because this record is not cleared for redistribution. photostimulation —causes→ rate photostimulation rate strength of the relation: 1 · note: a statistical definition rescued by the data's own shape - the definition WAS STATISTICAL, but the indices were BIMODAL, 0.045 against 0.76 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but light modulation indices compare firing during photostimulation with baseline; causes 'rate' is terse. Quotation withheld because this record is not cleared for redistribution. interneuron —causes→ pyramidal interneuron pyramidal strength of the relation: 1 · note: THE SAME LIGHT, THE OPPOSITE SIGN, DECIDED BY THE PROMOTER - identical parameters give pyramidal spiking in CaMKII::ChR2 and, in PV::ChR2, interneuron spiking FOLLOWED BY SILENCING of nearby pyramidal cells Audit 2026-09-28: DOUBTFUL - read against its span and kept, but PV-driven interneurons silenced nearby pyramidal cells; causes 'pyramidal' drops the silencing. Quotation withheld because this record is not cleared for redistribution. rate —contrasted-with→ temporal coding rate temporal coding strength of the relation: 1 · note: THE INSTRUMENT'S PURPOSE IS A DEBATE - the same debate Levi2022 would later call ROOTED IN DEFINITIONS Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span names the 'debate on rate vs. temporal coding'; contrasted-with is attributed. Quotation withheld because this record is not cleared for redistribution. diode —part-of→ silicon probe diode silicon probe strength of the relation: 1 · note: and the stated next step is to stop gluing - MEMS integration of diode dies with waveguides embedded IN the shanks Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but MEMS 'can be used to' integrate diode dies with a silicon probe's shanks; part-of is prospective. Quotation withheld because this record is not cleared for redistribution. Mann-Whitney U test Mann-Whitney U test Quotation withheld because this record is not cleared for redistribution. Wilcoxon signed-rank test Wilcoxon signed-rank test Quotation withheld because this record is not cleared for redistribution. chi-squared test chi-squared test Quotation withheld because this record is not cleared for redistribution. Kruskal-Wallis test Kruskal-Wallis test Quotation withheld because this record is not cleared for redistribution. exact binomial test exact binomial test Quotation withheld because this record is not cleared for redistribution. permutation test permutation test Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. principal component analysis principal component analysis Quotation withheld because this record is not cleared for redistribution. multiple-comparison correction multiple-comparison correction Quotation withheld because this record is not cleared for redistribution. regression regression Quotation withheld because this record is not cleared for redistribution. standard deviation standard deviation Quotation withheld because this record is not cleared for redistribution. standard error standard error Quotation withheld because this record is not cleared for redistribution. goodness of fit goodness of fit Quotation withheld because this record is not cleared for redistribution. U test U test Quotation withheld because this record is not cleared for redistribution. exact binomial test exact binomial test Quotation withheld because this record is not cleared for redistribution. permutation test permutation test Quotation withheld because this record is not cleared for redistribution. r 2 r 2 Quotation withheld because this record is not cleared for redistribution. L ratio L ratio Quotation withheld because this record is not cleared for redistribution. Weak blue light delivered through the fiber-coupled LEDs drove 42% of recorded hippocampal units (57 of 135) to change their firing rate in freely moving rats. Quotation withheld because this record is not cleared for redistribution. spike waveforms during light and during spontaneous activity were SIMILAR - median waveform consistencies 0.977 for light-modulated and 0.983 for nonresponsive units, U test P = 0.19 Quotation withheld because this record is not cleared for redistribution. units recorded on the illuminated shank were often modulated, 20/39 units or 52%, whereas the fraction of modulated units on other shanks was AT CHANCE LEVEL Quotation withheld because this record is not cleared for redistribution. Light-evoked spiking was temporally precise, with a median across-trial jitter of 2 ms. Quotation withheld because this record is not cleared for redistribution. Blue light with identical parameters in CA1 of PV::ChR2 mice drove interneurons to spike and then silenced nearby pyramidal cells. Quotation withheld because this record is not cleared for redistribution. reliable activation of units on shank 1 during blue light pulses and robust silencing of THE SAME UNITS during the red light pulses Quotation withheld because this record is not cleared for redistribution. An index-matching coupling medium at the diode-fiber interface doubled the light output, to 30-50 microwatts for blue LEDs. Quotation withheld because this record is not cleared for redistribution. these units exhibited phase precession Quotation withheld because this record is not cleared for redistribution. the mean scattering coefficients depended on wavelength Quotation withheld because this record is not cleared for redistribution. the fraction of significantly light-modulated units exhibited a marked increase between 3.5 and 5.5 mW/mm 2, from 15 to 73% Quotation withheld because this record is not cleared for redistribution. THE PAPER'S HEADLINE ADVANTAGE, RE-TAGGED AS A LIMITATION: spatially restricted photostimulation IS ACTUALLY A LIMITATION where synchronous control of an entire structure is wanted Quotation withheld because this record is not cleared for redistribution. and the resolution is a question, not a setting - THE SPECIFIC LIGHT SOURCES AND FIBERS SHOULD BE TAILORED TO THE SCIENTIFIC QUESTION AT HAND Quotation withheld because this record is not cleared for redistribution. ONE INTERVENTION, OPPOSITE SIGNS: the index-matching glue cuts reflective losses to under 1% BUT AT A COST OF REDUCING the acceptance angle BY 41% Quotation withheld because this record is not cleared for redistribution. while its effect on the skew rays acceptance angle is DIAMETRICALLY OPPOSITE, giving A TWOFOLD INCREASE in coupling efficiency Quotation withheld because this record is not cleared for redistribution. A MEASURED CONSTANT DISAGREEING WITH THE PUBLISHED ONE: blue-light scattering 7.18 against a reported 10.3, and IN ANY EVENT the estimates were SIMILAR REGARDLESS OF THE PRECISE NUMBER USED Quotation withheld because this record is not cleared for redistribution. the fitted model CONSISTENTLY OVERESTIMATED power beyond 1 mm and ran 5 to 10% off in nonfresh tissue Quotation withheld because this record is not cleared for redistribution. WHY THE LIGHT MUST BE WEAK AND CLOSE: stimulating further away INEVITABLY ACTIVATES MANY MORE UNMONITORED NEURONS THAN ARE BEING MONITORED, MAKING THE SEPARATION BETWEEN DIRECT AND POPULATION-MEDIATED EFFECTS IMPOSSIBLE Quotation withheld because this record is not cleared for redistribution. and strong light of ANY wavelength adds HEAT with a MIXED DE-/HYPERPOLARIZING effect, a confound independent of the opsin Quotation withheld because this record is not cleared for redistribution. THE SAME LIGHT, THE OPPOSITE SIGN, DECIDED BY THE PROMOTER: pyramidal cells spike in CaMKII::ChR2 mice and are SILENCED in PV::ChR2 mice under identical parameters Quotation withheld because this record is not cleared for redistribution. A 25% CHANGE IN DOSE FLIPS THE OUTCOME: 70% of 0.35 mW/mm 2 pulses efficient against 10% of 0.28 mW/mm 2 pulses Quotation withheld because this record is not cleared for redistribution. the statistical definition of light modulation is rescued by a BIMODAL distribution of the indices, 0.045 against 0.76 Quotation withheld because this record is not cleared for redistribution. with the response fraction hedged - it MAY BE DUE TO transduction rates and the proximity of the fiber tip Quotation withheld because this record is not cleared for redistribution. THE UNIT IS DEFINED BY NUMBERED GATES BEFORE ANY RESULT: amplitude, L ratio, refractory period, then a firing floor that cut 535 hippocampal units to 135 Quotation withheld because this record is not cleared for redistribution. an idealisation declared inside a figure legend - ASSUMES neuronal density of 20,000 cells/mm 3 and IGNORES SHADOWING by the probe shank Quotation withheld because this record is not cleared for redistribution. the empirical light map is declared A PROXY ONLY, since scattering contributes ESPECIALLY AT SHORT WAVELENGTHS Quotation withheld because this record is not cleared for redistribution. NATIVE NETWORK DYNAMICS CAN INCORPORATE SYNTHETIC PATTERNS OF ACTIVITY - units driven by nonperiodic photostimuli exhibited PHASE PRECESSION Quotation withheld because this record is not cleared for redistribution. and the whole device exists to remove one number - a freely moving animal can be tethered to ONE OR TWO fibers, which RESTRICTED the questions that could be addressed Quotation withheld because this record is not cleared for redistribution. diode-probe system diode-probe system Quotation withheld because this record is not cleared for redistribution. light-modulated unit light-modulated unit Quotation withheld because this record is not cleared for redistribution. light modulation index light modulation index Quotation withheld because this record is not cleared for redistribution. waveform consistency waveform consistency Quotation withheld because this record is not cleared for redistribution. center-of-mass center-of-mass Quotation withheld because this record is not cleared for redistribution. spiking probability spiking probability Quotation withheld because this record is not cleared for redistribution. closed-loop control closed-loop control Quotation withheld because this record is not cleared for redistribution. threshold threshold Quotation withheld because this record is not cleared for redistribution. coupling coupling Quotation withheld because this record is not cleared for redistribution. unit unit Quotation withheld because this record is not cleared for redistribution. precision precision Quotation withheld because this record is not cleared for redistribution. light intensity light intensity Quotation withheld because this record is not cleared for redistribution. Firing rate during light Firing rate during light Quotation withheld because this record is not cleared for redistribution. spiking probability spiking probability Quotation withheld because this record is not cleared for redistribution. baseline period baseline period Quotation withheld because this record is not cleared for redistribution. intensity intensity Quotation withheld because this record is not cleared for redistribution. precision precision Quotation withheld because this record is not cleared for redistribution. rate rate Quotation withheld because this record is not cleared for redistribution. coupling coupling Quotation withheld because this record is not cleared for redistribution. 42%; 57/135 — Fraction and count of hippocampal units whose firing rate was modulated by weak blue light Quotation withheld because this record is not cleared for redistribution. median, 2 ms — Across-trial standard deviation of spike centers-of-mass, i.e. the temporal precision of light-evoked spiking Quotation withheld because this record is not cleared for redistribution. median, 5.5 ms — Median latency from light onset to the first significantly elevated PSTH bin Quotation withheld because this record is not cleared for redistribution. ∼0.001 mm 3 — Volume of brain tissue illuminated above the ChR2 activation threshold by a single fiber Quotation withheld because this record is not cleared for redistribution. 20–100 — Estimated number of neurons inside the illuminated volume, given assumed cortical cell density Quotation withheld because this record is not cleared for redistribution. 0.1–0.15% — Diode-to-fiber coupling efficiency for blue LEDs before index matching, versus about 2.5% for laser diodes Quotation withheld because this record is not cleared for redistribution. 100–130 mg — Weight of a single diode-fiber assembly, which is what keeps the headgear light enough for free movement Quotation withheld because this record is not cleared for redistribution. 0.5–1.5 g — Weight of a complete implantation-ready multidiode device Quotation withheld because this record is not cleared for redistribution. 535 hippocampal and 98 neocortical units — Total number of single units isolated that met the amplitude and isolation criteria Quotation withheld because this record is not cleared for redistribution. 1.82 — Median ratio of spiking probability during blue light to duration-matched spontaneous periods Quotation withheld because this record is not cleared for redistribution. 70% ... 10% — Fraction of blue pulses able to break through halorhodopsin silencing at 0.35 versus 0.28 mW/mm2, showing a sharp intensity threshold Quotation withheld because this record is not cleared for redistribution. 0.001 mm 3 — the illuminated volume, and the paper's unit of claim - the tissue a shank of a silicon probe can also monitor Quotation withheld because this record is not cleared for redistribution. 7.18 ± 0.17 — the scattering coefficient measured for blue light, against a previously reported 10.3 for rat brain Quotation withheld because this record is not cleared for redistribution. 41% — the acceptance angle the index-matching glue COSTS, at the same time as it removes the reflective losses Quotation withheld because this record is not cleared for redistribution. 2 ms — the temporal precision of light-evoked spiking, the across-trial SD of the centers-of-mass Quotation withheld because this record is not cleared for redistribution. 70% — the fraction of 0.35 mW/mm 2 blue pulses that overcame the red-light hyperpolarization, against 10% at 0.28 Quotation withheld because this record is not cleared for redistribution. 20,000 cells/mm 3 — the neuronal density ASSUMED by the illuminated-cell estimate, in a legend that also says it ignores shadowing Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1152/jn.00153.2012.