Millisecond-Timescale, Genetically Targeted Optical Control of Neural Activity
Nature Neuroscience, 2005 · paper · Biomedicine
Adapts the algal light-gated channel Channelrhodopsin-2, delivered by lentivirus, to let light control mammalian neurons. It demonstrates millisecond-timescale control of neuronal spiking and of excitatory and inhibitory synaptic transmission.
Checked: PDF from synthneuro.org, fetched 4 Oct 2026. Page numbers are those of that PDF.
1 finding
Reference or label Methods: "For all experiments except for the synaptic transmission data shown in Figure 4b,c" — the synaptic transmission data are in Figure 4c,d; panel 4b shows subthreshold depolarizations.
- p. 6 Methods, Electrophysiology and optical methods, first paragraph on page
transmission data shown in Figure 4b,c, we patched
- p. 4 Figure 4 legend
(b) Repeated light pulses induced reliable depolarizations. (c) Excitatory synaptic
- p. 4 Results, Remote activation of subthreshold and synaptic responses
both excitatory (Fig. 4c) and inhibitory (Fig. 4d) synaptic
- p. 6 Methods, Electrophysiology and optical methods, first paragraph on the page
transmission data shown in Figure 4b,c
Judge's note: Page 6 image shows "Figure 4b,c". On the page 4 image, panel b is unlabelled depolarization traces (legend: "(b) Repeated light pulses induced reliable depolarizations"), panel c is titled "Excitatory synaptic transmission" and panel d "Inhibitory synaptic transmission". The Results cite "excitatory (Fig. 4c) and inhibitory (Fig. 4d) synaptic events". The pointer should read Figure 4c,d.
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8 minor (typos and the like; most checked by the judge only)
Reference or label "As expected from the observation that light pulses generally elicited single spikes (Figs. 1d and 2)" cites Fig. 1d, which shows 1-s steady illumination evoking several spikes; the brief-pulse panel is Fig. 1e.
- p. 3 Results, right column, frequency-response paragraph
generally elicited single spikes (Figs. 1d and 2)
- p. 1 Figure 1 legend
(e) Voltage traces in response to brief light pulse series
- p. 2 Results, steady illumination paragraph
any subsequent spikes elicited during steady illumination were poorly timed (Fig. 1d, left)
- p. 1 Figure 1 legend
1-s periods of light (gray bar)
Only the authors can say what is right here.
Judge's note: On the page 1 image, panel d shows traces with multiple spikes under a 1-s light bar, and the legend says "1-s periods of light". Panel e shows the brief pulse series. The text on page 3 itself cites Fig. 1e for "Longer light pulses evoked single spikes". Fig. 1d (right) does analyse the single reliable first spike, so a loose intended reading is possible. For that reason this is a query to the authors (probably Fig. 1e) and not a firm correction.
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Wording The λ = 200 ms stimulus is described as "a second series (mean interval λ = 200 ms) comprising 46 spikes" and Fig. 2g is titled "59 spikes" / "46 spikes", although 59 and 46 are counts of light pulses ("59-pulse-long series"; "31/59 light pulses ... 30/46 light pulses").
- p. 3 Results, Precise spike trains
a second series (mean interval λ = 200 ms) comprising 46 spikes
- p. 3 Results, Precise spike trains
repeated 59-pulse-long series of light pulses
- p. 2 Figure 2g panel titles
46 spikes
- p. 6 Methods, Data analysis
30/46 light pulses for the
Judge's note: Page 3 image: "59-pulse-long series of light pulses" and "comprising 46 spikes" are in the same paragraph. Page 2 image: Fig. 2g panel titles read "λ = 100, 59 spikes" and "λ = 200, 46 spikes". Page 6 Methods use "light pulses" for both counts. With 76% and 85% fidelity the evoked spike counts would be about 45 and 39, not 59 and 46. "Spikes" may be shorthand for intended spike times (the Fig. 2g x-axis reads "# of neurons firing a given spike"), so this is a wording inconsistency and not a data error.
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Wording Discussion says "Because ChR2 is encoded by a single open reading frame of only 315 amino acids", whereas the Introduction says "The N-terminal 315 amino acids of ChR2" and the Methods say "the first 315 amino acid residues of ChR2", i.e. 315 residues is only part of ChR2.
- p. 5 Discussion, third paragraph
Because ChR2 is encoded by a single open reading frame of only 315
- p. 2 Introduction
The N-terminal 315 amino acids of ChR2 are
- p. 5 Methods, Plasmid constructs
the first 315 amino acid residues of
Only the authors can say what is right here.
Judge's note: Read all three passages on the page 2 and page 5 images. The Introduction and Methods treat the 315 residues as the N-terminal fragment of a longer protein, which is what was fused to YFP. The Discussion gives 315 amino acids as the size of the ChR2 open reading frame. The authors probably mean the functional fragment used in the construct, but as worded the statements do not agree. No full length is given in the paper, so only the authors can say which wording is intended.
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Typo Figure 1b legend repeats the position word: "right, population data (right; mean ± s.d. plotted throughout; n = 18)".
- p. 1 Figure 1 legend, panel b
right, population data (right; mean ± s.d. plotted
Judge's note: Read the Figure 1 legend on the page 1 image. "right" appears twice for the same sub-panel; there is only one population-data plot in panel b. Cosmetic duplication.
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Typo Introduction cites consecutive references as "although elegant8–10,11", while the Discussion cites the same set as "stimulation methods8–11".
- p. 1 Introduction, second paragraph
although elegant8–10,11
- p. 5 Discussion, first paragraph
stimulation methods8–11
Judge's note: Page 1 image shows the superscript as 8–10,11; page 5 image shows 8–11. The references are the same four (8, 9, 10, 11), so this is a formatting inconsistency only.
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Typo Protein name misspelled: "Channelrhododopsin-2 (ChR2), is a light-gated cation channel"; it is "Channelrhodopsin-2" in the abstract and in reference 12.
- p. 2 Introduction, second paragraph on page
Channelrhododopsin-2 (ChR2)
- p. 2
Channelrhododopsin-2 (ChR2), is a light-
Judge's note: The page 2 image shows "Channelrhododopsin-2" in the typeset text, so it is not an extraction artefact. The abstract (page 1) and reference 12 (page 6) spell it "Channelrhodopsin-2".
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Typo Redundant unit: "(76% and 85% percent of light pulses successfully evoked spikes, respectively; Fig. 2d)".
- p. 3 Results, Precise spike trains, end of left column
(76% and 85% percent of light pulses
- p. 3
76% and 85% percent of light pulses
Judge's note: Visible on the page 3 image at the bottom of the left column: the percent sign is followed by the word "percent".
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Typo Missing closing parenthesis after n = 12: "(178 ± 81 MΩ; Fig. 5a; P > 0.35; n = 12 and resting potential (−59.7 ± 7.0 mV; Fig. 5b; P > 0.75)."
- p. 4 Results, Expression of ChR2 has minimal side effects, second paragraph
(178 ± 81 MΩ; Fig. 5a; P > 0.35; n = 12 and resting potential (−59.7 ±
- p. 4 Results, light-exposed neurons paragraph
(178 ± 81 MO; Fig. 5a; P 4 0.35; n ¼ 12 and resting potential
Judge's note: On the page 4 image the parenthesis opened before "178 ± 81 MΩ" is not closed before "and resting potential (". The parallel sentence earlier in the section is punctuated correctly ("n = 18 each) or resting potential").
Second check: none (judge only)