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DANDI:001933

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Leucine-rich repeat kinase 2 impairs the release sites of Parkinson’s disease vulnerable dopamine axons

behavioral House mouse Converted by CatalystNeuro 570 MB 27 files
  • 6 reproduced
  • 2 partially reproduced
  • 1 not reproduced

Counted separately: 8 claims on data the paper deposited in other archives.

  • 8 blocked

Counted separately: 1 check that the dataset is the data behind the paper.

  • 1 not reproduced

An earlier attempt. Attempt 001933-chen-2026-02 replaced it; the dataset’s page shows the current outcomes. Its notebooks link to the entry as it is now, which the later attempt updated; the attempt record is as it was.

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Claims

From the paper Leucine-rich repeat kinase 2 impairs the release sites of Parkinson’s disease vulnerable dopamine axons

Reproducing Chen, He et al. (2026) from dandiset 001933 10

Notebook reproduce_chen_2026.ipynb

  • Not reproducedResults, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    The G2019S reduction of evoked release at 0.5 mW is much larger for Anxa1+ (Cohen's d = 2.05) than for Calb1+ stimulation (d = 0.76).

    the magnitude of this reduction was far smaller than that observed in the Anxa1+ subtype experiments(Fig. 6C and Supplementary Fig. 8E, Cohen’s D, D(Anxa1 + , 0.5 mW) = 2.05, D(Calb1 + , 0.5 mW) = 0.76)

    Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    Anxa1 d = 2.21 is within tolerance; Calb1 d = 1.40 is not (0.684 to 0.836), and the ratio 1.58 is under the factor of 2 the criterion asks. With the code's window, 2.06 and 1.25. The paper's published integrals give 2.06 and 0.765, so the miss is consistent with the Calb1 dF/F in the dandiset not being the paper's. The Anxa1 effect is larger than the Calb1 effect at every power and window that starts by onset (ratio 1.29 to 1.74), so the direction of the paper's comparison holds, with a smaller gap.

    How the test differed from the paper’s method

    • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
  • Partially reproducedFigure 6F (right) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    Six of eight individual G2019S mice show significantly smaller spontaneous dopamine transients than the WT group; mice 4651 and 3743 do not.

    Specifically, six out of eight individual LRRK2G2019S mice showed a statistically significant reduction in spontaneous dopamine release compared to the control group (Fig. 6F).

    Figure 6F (right) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    What the paper reports

    • mouse 4885 against the WT group: one-tailed, two sampled t-test, p = 1.4 × 10⁻⁴⁹ (n = the mouse's transients against the WT group)
    • mouse 4651 against the WT group: one-tailed, two sampled t-test, p = 0.008 (n = the mouse's transients against the WT group)
    • mouse 4652 against the WT group: one-tailed, two sampled t-test, p = 6.2 × 10⁻¹³ (n = the mouse's transients against the WT group)
    • mouse 3742 against the WT group: one-tailed, two sampled t-test, p = 5.3 × 10⁻⁸⁸ (n = the mouse's transients against the WT group)
    • mouse 3743 against the WT group: one-tailed, two sampled t-test, p = 0.97 (n = the mouse's transients against the WT group)
    • mouse 4004 against the WT group: one-tailed, two sampled t-test, p = 1.2 × 10⁻⁹⁵ (n = the mouse's transients against the WT group)
    • mouse 4005 against the WT group: one-tailed, two sampled t-test, p = 4.1 × 10⁻¹⁰⁹ (n = the mouse's transients against the WT group)
    • mouse 4007 against the WT group: one-tailed, two sampled t-test, p = 5 × 10⁻¹⁰⁷ (n = the mouse's transients against the WT group)

    By the integral 5 of 8 GS mice are below the WT group under every reading; the exceptions are 3743 (p = 0.431), 4651 (mean 417, above the WT mean of 303) and 4652 (p = 0.0128). With the transient mean, the paper's measure, the one-tailed Student test gives 6 of 8 with 3743 and 4651 as the exceptions and p-values close to the legend's (4651 0.00819 against 0.008, 3742 5.38e-88 against 5.28e-88); the Welch tests give 7 there. The difference from the paper comes from the measure; the paper's count follows the Student test of its legend.

    How the test differed from the paper’s method

    • The integral of each transient is used, as the Methods state; the paper's measure is shown as a variant.
  • Partially reproducedSupplementary Figure 8E (right); Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    Only 2 of 7 G2019S mice show reduced Calb1+ evoked dopamine release relative to the WT group.

    with only 2 out of 7 LRRK2G2019S mice showing a reduction in Calb1+ evoked DA release relative to WT controls (Supplementary Fig. 8E).

    Supplementary Figure 8E (right); Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    At 0.5 mW, 7 (Welch one-tailed), 6 (Welch two-tailed) and 4 (Student, either tail) of 7 GS mice are below the WT group at p < 0.05/7, against the paper's 2; the closest reading gives 4, recorded as measured. Student tests give 2 at 0.1 and 1 mW. The panel's power is not stated, and the dandiset's Calb1 dF/F is not the paper's.

    How the test differed from the paper’s method

    • The legend does not state the power of the per-mouse panel; 0.5 mW was fixed before the analysis and the other powers are shown.
    • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
  • ReproducedFigure 6E (left) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    Optogenetically evoked dopamine release in the dorsolateral striatum (Anxa1+ projection region) at 0.5 mW is lower in LRRK2-G2019S than in LRRK2-WT mice (64 against 56 stimulations, p = 1.10e-20, one-tailed two-sample t-test).

    We found that evoked dopamine release was significantly reduced in LRRK2G2019S compared to LRRK2WT mice (Fig. 6D, E) ... Left, group-level comparisons (LRRK2G2019S n = 64 stimulations, WT n = 56 stimulations

    Figure 6E (left) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    What the paper reports

    • one-tailed, two-sampled t-test, p = 1.1 × 10⁻²⁰ (n = 64 G2019S and 56 WT stimulations)

    Light-on integrals at 0.5 mW, GS 48.8 against WT 128.0 % dF/F x s, one-tailed p = 1.16e-22 (paper 1.10e-20), Cohen's d 2.21. The code's window gives p = 1.1e-20, the paper's value. It holds at 4 mW (p = 4.08e-18), without the two GS mice given 0.33 s trains (p = 4.16e-17), and with mouse means (Welch p = 0.000434). The window chunking_index.m computes as written reverses the sign (p = 1).

    How the test differed from the paper’s method

    • The integral is over each train's light-on period, as the Methods state; the paper's values come from the code's window, -0.1 to 1.0 s, shown as a variant. The baseline, which the Methods do not give, is the code's.
    • The paper's plotting code selects power code 'h' for this panel; the panel is tested at the 0.5 mW of the legend, which the source data confirm, and 4 mW is shown as a variant.
  • ReproducedFigure 6E (right) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    Seven of eight individual G2019S mice show significantly reduced evoked dopamine release at 0.5 mW compared with the WT group; mouse 3743 does not.

    Specifically, 7 out of 8 individual LRRK2G2019S mice showed a statistically significant reduction in dopamine release compared to the control group (Fig. 6E).

    Figure 6E (right) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    What the paper reports

    • mouse 4885 against the WT group: one-tailed, two sampled t-test, p = 2.6 × 10⁻¹⁰ (n = 8 stimulations of the mouse against the WT group)
    • mouse 4651 against the WT group: one-tailed, two sampled t-test, p = 4 × 10⁻⁴ (n = 8 stimulations of the mouse against the WT group)
    • mouse 4652 against the WT group: one-tailed, two sampled t-test, p = 7.4 × 10⁻⁵ (n = 8 stimulations of the mouse against the WT group)
    • mouse 3742 against the WT group: one-tailed, two sampled t-test, p = 4.1 × 10⁻¹⁵ (n = 8 stimulations of the mouse against the WT group)
    • mouse 3743 against the WT group: one-tailed, two sampled t-test, p = 0.477797 (n = 8 stimulations of the mouse against the WT group)
    • mouse 4004 against the WT group: one-tailed, two sampled t-test, p = 2.8 × 10⁻¹³ (n = 8 stimulations of the mouse against the WT group)
    • mouse 4005 against the WT group: one-tailed, two sampled t-test, p = 1.7 × 10⁻¹⁴ (n = 8 stimulations of the mouse against the WT group)
    • mouse 4007 against the WT group: one-tailed, two sampled t-test, p = 2.4 × 10⁻¹² (n = 8 stimulations of the mouse against the WT group)

    Under all four readings (Welch or Student, one- or two-tailed) 7 of 8 GS mice are below the WT group at p < 0.05/8 and 3743 is the exception (mean 125 against 128, Welch one-tailed p = 0.362). The count is the same with the code's window. Two of the seven, 3742 and 4885, received the paper's powers as 0.33 s trains, unlike every WT mouse, and their responses do not follow the labelled power; the other five significant mice were stimulated as the WT mice were.

    How the test differed from the paper’s method

    • The Methods name Welch's test, the legend's p-values are one-tailed and the code runs a two-tailed Student test; all four readings are shown and all give 7.
  • ReproducedSupplementary Figure 7C; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    The reduction of evoked dopamine release in Anxa1 G2019S mice holds at each of the four stimulation powers, 0.1, 0.5, 1 and 4 mW (p from 1.29e-15 to 1.10e-20).

    This reduction was observed across a range of optogenetic stimulation powers (Supplementary Fig. 7B, C).

    Supplementary Figure 7C; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    What the paper reports

    • 0.1 mW: one-tailed, two-sampled t-test, p = 1.3 × 10⁻¹⁵ (n = 64 G2019S and 56 WT stimulations)
    • 0.5 mW: one-tailed, two-sampled t-test, p = 1.1 × 10⁻²⁰ (n = 64 G2019S and 56 WT stimulations)
    • 1 mW: one-tailed, two-sampled t-test, p = 1.2 × 10⁻¹⁷ (n = 64 G2019S and 56 WT stimulations)
    • 4 mW: one-tailed, two-sampled t-test, p = 2.4 × 10⁻¹⁶ (n = 64 G2019S and 56 WT stimulations)

    GS lower at all four powers, one-tailed p from 3.13e-15 to 1.16e-22 with the light-on window. With the code's window the p-values at 0.1, 0.5 and 1 mW equal the paper's (1.29e-15, 1.1e-20, 1.22e-17); at 4 mW it is 5.62e-16 against 2.39e-16, as that window, which runs to 1.0 s after onset, leaves 55 WT stimulations there (the processed series of mouse 4398 ends 0.8 s after its last onset). The Methods window keeps all 56.

    How the test differed from the paper’s method

    • In the code's window variant, 55 WT stimulations at 4 mW in place of 56, as one falls at the end of a truncated series.
  • ReproducedFigure 6F (left) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    Spontaneous dopamine transients in the dorsolateral striatum are smaller in G2019S than in WT mice (1064 against 798 transients, p = 2.75e-177, one-tailed two-sample t-test), with 57 to 285 transients per mouse.

    spontaneous dopamine release in this Anxa1+ dopamine subtype projection region of the DLS was also significantly reduced in LRRK2G2019S compared to LRRK2WT mice (Fig. 6F) ... (LRRK2G2019S n = 1064 transients, WT n = 798 transients ... n = 57–285 transients/mouse

    Figure 6F (left) and legend; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 1

    What the paper reports

    • one-tailed, two-sampled t-test, p = 2.7 × 10⁻¹⁷⁷ (n = 1064 G2019S and 798 WT transients)

    The Methods' detection gives the paper's counts exactly (1064 and 798, 57 to 285 per mouse). Integrals GS 131.9 against WT 302.9 % dF/F x s, one-tailed p = 4.85e-72 (paper 2.75e-177). With the mean dF/F over each transient, the measure of the published values, p = 2.23e-177. With mouse means, Welch p = 0.0318.

    How the test differed from the paper’s method

    • The integral of each transient is used, as the Methods state; the paper's values are 0.005 times the mean dF/F over the transient, shown as a variant.
  • ReproducedSupplementary Figure 8C; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    In the dorsomedial striatum (Calb1+ projection region), spontaneous dopamine transients are not reduced in G2019S mice (970 against 682 transients, p = 0.98).

    spontaneous dopamine release in this region of the DMS was not significantly reduced in LRRK2G2019S mice compared to LRRK2WT mice (Supplementary Fig. 8C, p = 0.98)

    Supplementary Figure 8C; Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    What the paper reports

    • one-tailed, two-sampled t-test, p = 0.98 (n = 970 G2019S and 682 WT transients)

    The paper's test does not find the effect, one-tailed p = 0.0509, difference of means 21.1 % dF/F x s, Cohen's d 0.085; the result sits at the threshold. With the transient mean GS are lower at p = 2.25e-09 (d 0.306), with the code's exclusion window as written at p = 1.81e-05, and with mouse means Welch p = 0.402. The counts are within tolerance but differ from the paper's 970 and 682, and the Calb1 dF/F in the dandiset is not the one the paper analysed (source-data-link); the published values give p = 0.989.

    How the test differed from the paper’s method

    • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.
  • ReproducedSupplementary Figure 8E (left); Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    Evoked dopamine release in the dorsomedial striatum from Calb1+ neuron stimulation is reduced in G2019S mice at each of four powers (56 against 40 stimulations per power, p from 6.45e-05 to 0.001).

    While optogenetically evoked dopamine release in the DMS from Calb1+ neuron stimulation was significantly reduced in LRRK2G2019S mice compared to LRRK2WT across multiple stimulation powers (Supplementary Fig. 8D, E)

    Supplementary Figure 8E (left); Results, In vivo dopamine release is reduced in the Anxa1+ subtype projection region of striatum in LRRK2G2019S compared to control mice, paragraph 2

    What the paper reports

    • 0.1 mW: one-tailed, two-sampled t-test, p = 6.4 × 10⁻⁵ (n = 56 G2019S and 40 WT stimulations)
    • 0.5 mW: one-tailed, two-sampled t-test, p = 2 × 10⁻⁴ (n = 56 G2019S and 40 WT stimulations)
    • 1 mW: one-tailed, two-sampled t-test, p = 10⁻⁴ (n = 56 G2019S and 40 WT stimulations)
    • 4 mW: one-tailed, two-sampled t-test, p = 0.001 (n = 56 G2019S and 40 WT stimulations)

    GS lower at all four powers, one-tailed p from 4.38e-07 to 6.29e-10, smaller than the paper's 6.45e-05 to 0.001. The p-values differ because the dandiset's Calb1 dF/F is not the paper's (source-data-link). With one value per mouse (7 GS, 5 WT), Welch one-tailed p is 0.0424, 0.0413, 0.0726 and 0.0916 at 0.1, 0.5, 1 and 4 mW.

    How the test differed from the paper’s method

    • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.

Not tested in a notebook 8

8 data missing from the dataset
  • BlockedFigure 1B and 1D; Results, LRRK2 is expressed in dopamine neurons and is enriched in the vulnerable subpopulation of neurons, paragraph 3· Data missing from the datasetdata in BioImage Archive S-BIAD2070 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

    LRRK2 immunolabeling intensity is higher in Aldh1a1+ (vulnerable) than in Aldh1a1- SNc dopamine neurons (p = 0.0008).

    quantification of our immunolabeling experiments indicated that LRRK2 protein expression was higher in the most vulnerable dopamine neuron populations in the mouse brain, specifically those of the ventral tier SNc, marked by Aldh1a1 (Fig. 1D).

    Figure 1B and 1D; Results, LRRK2 is expressed in dopamine neurons and is enriched in the vulnerable subpopulation of neurons, paragraph 3

    What the paper reports

    • two-tailed unpaired t-test, p = 8 × 10⁻⁴ (n = 16 sections from 3 mice)

    The immunostaining images are not in the dandiset, which holds only the photometry. They are in the BioImage Archive (S-BIAD2070, S-BIAD2071, S-BIAD2072 and S-BIAD2074) and per-section values in the Zenodo source data.

  • BlockedFigure 2A to 2C; Results, LRRK2 phosphorylates RAB3 isoforms in vivo, paragraphs 1 and 2· Data missing from the datasetdata in PRIDE PXD065006

    LRRK2 kinase inhibition with MLi-2 changes 289 phosphopeptides in striatal synaptosomes of G2019S mice, including RAB3 T86.

    we identified 289 significantly altered phosphopeptides (Fig. 2B, supplementary data 1) ... the decreased phosphorylation at the T86 site of the RAB3 GTPase in LRRK2G2019S mice treated with MLi-2, compared to the vehicle group (Fig. 2B).

    Figure 2A to 2C; Results, LRRK2 phosphorylates RAB3 isoforms in vivo, paragraphs 1 and 2

    The phosphoproteomics are not in the dandiset; they are in PRIDE (PXD065003, PXD065006, PXD065125).

  • BlockedFigure 2D to 2G; Results, LRRK2 phosphorylates RAB3 isoforms in vivo, paragraph 4· Data missing from the datasetdata in Zenodo doi:10.5281/zenodo.19930567

    Phosphorylation of RAB3A and RAB3C is increased in the SNc of G2019S mice and returns to WT levels with MLi-2.

    The slower migrating RAB3A band ... was increased in the SNc of LRRK2G2019S mice as compared to littermate controls. This increase returned to wild-type levels when the LRRK2G2019S mice were treated with MLi-2 ... an increase in phosphorylated RAB3C protein was observed in the mutant LRRK2 compared to the wild type, which was reversed upon MLi-2 treatment

    Figure 2D to 2G; Results, LRRK2 phosphorylates RAB3 isoforms in vivo, paragraph 4

    What the paper reports

    • p-RAB3A, WT against GS: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0202, Šídák-corrected (n = 10 mice per treatment)
    • p-RAB3A, GS against GS with MLi-2: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0069, Šídák-corrected (n = 10 mice per treatment)
    • p-RAB3C, WT against GS: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0036, Šídák-corrected (n = 7 mice per treatment)
    • p-RAB3C, GS against GS with MLi-2: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0415, Šídák-corrected (n = 7 mice per treatment)

    The western blots are not in the dandiset; blot images and values are in the Zenodo source data.

  • BlockedFigure 3D to 3F; Results, Phosphorylation of RAB3A decreases its binding to the effector proteins RIM1 and RIM2 from mouse brain, paragraph 2· Data missing from the datasetdata in PRIDE PXD065125

    RIM1 and RIM2 bind unphosphorylated RAB3A in preference to RAB3A phosphorylated at T86, while RILPL1 and RILPL2 prefer the phosphorylated form.

    The RAB3A effector proteins RIM1 and RIM2 showed a marked preference for binding to unphosphorylated RAB3A (Fig. 3D, E) ... Conversely, we found that p-RAB3A preferentially associated with RILPL1 and RILPL2 (Fig. 3D, F)

    Figure 3D to 3F; Results, Phosphorylation of RAB3A decreases its binding to the effector proteins RIM1 and RIM2 from mouse brain, paragraph 2

    What the paper reports

    • RIM2, RAB3A against p-RAB3A: paired two-sided Student’s t-test, p = 0.011 (n = 6 replicates per condition)
    • RILPL1, p-RAB3A against RAB3A: paired two-sided Student’s t-test, p = 0.002 (n = 6 replicates per condition)

    The affinity purification mass spectrometry is not in the dandiset; it is in PRIDE.

  • BlockedFigure 4D and 4E; Results, LRRK2 alters the composition and organization of active zone release sites in dopaminergic striatal synaptosomes, paragraph 2· Data missing from the datasetdata in BioImage Archive S-BIAD2074 (images); Zenodo doi:10.5281/zenodo.19930567 (per-area values)

    Fewer TH+/VAMP2+ striatal synaptosomes from G2019S mice contain bassoon, and the remaining bassoon clusters are larger.

    we found a significant decrease in the percentage of TH + /VAMP2+ synaptosomes that contained the active zone marker bassoon (Fig. 4D). In addition, the remaining active zone clusters in LRRK2G2019S TH + /VAMP2+ synaptosomes had an increased average area of bassoon staining when compared to wildtype (Fig. 4E)

    Figure 4D and 4E; Results, LRRK2 alters the composition and organization of active zone release sites in dopaminergic striatal synaptosomes, paragraph 2

    What the paper reports

    • percentage of TH+/VAMP2+ synaptosomes with bassoon: two-tailed unpaired t-test, p < 10⁻⁴ (n = 39 WT areas from 3 mice and 35 G2019S areas from 3 mice)
    • bassoon area: two-tailed unpaired t-test, p = 0.0301 (n = 43 WT areas from 4 mice and 57 G2019S areas from 4 mice)

    The synaptosome images are not in the dandiset; they are in the BioImage Archive.

  • BlockedFigure 4H to 4L; Results, LRRK2 alters the composition and organization of active zone release sites in dopaminergic striatal synaptosomes, paragraph 3· Data missing from the datasetdata in Zenodo doi:10.5281/zenodo.19930567

    RIM1 is reduced in striatal synaptosomes of G2019S mice (p = 0.0245) but not in other striatal fractions or the SNc.

    However, we observed a decrease in RIM1 levels in the LRRK2G2019S synaptosome fraction compared to controls (Fig. 4I and Supplementary Fig. 4F). In contrast, RIM1 levels in other striatal fractions or SNc lysates did not change (Fig. 4J–L)

    Figure 4H to 4L; Results, LRRK2 alters the composition and organization of active zone release sites in dopaminergic striatal synaptosomes, paragraph 3

    What the paper reports

    • two-tailed unpaired t-test, p = 0.0245 (n = 6 mice per genotype)

    The western blots are not in the dandiset; they are in the Zenodo source data.

  • BlockedFigure 5D, 5E, 5G and 5H; Results, LRRK2 disrupts the number and composition of active zone release sites in vulnerable dopamine axons, paragraph 1· Data missing from the datasetdata in BioImage Archive S-BIAD2071 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

    Bassoon cluster density is reduced and cluster volume increased in Aldh1a1+ but not Aldh1a1- dopamine axons of G2019S mice, and the same holds in Anxa1+ axons.

    We observed a decrease in the density of bassoon+ clusters in vulnerable Aldh1a1+ but not resilient Aldh1a1- axons of LRRK2G2019S, compared to LRRK2WT mice (Fig. 5D) ... an increase in the volume of the remaining bassoon clusters in Aldh1a1+ but not Aldh1a1- dopamine axons ... We confirmed these findings using an independent mouse line, Anxa1Cre (Fig. 5F–H).

    Figure 5D, 5E, 5G and 5H; Results, LRRK2 disrupts the number and composition of active zone release sites in vulnerable dopamine axons, paragraph 1

    What the paper reports

    • Aldh1a1+ bassoon cluster density, GS against WT: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0344, Šídák-corrected
    • Aldh1a1+ bassoon cluster volume, GS against WT: Šídák’s multiple comparisons test following a two-way ANOVA, p = 0.0385, Šídák-corrected
    • Anxa1 bassoon cluster density: two-tailed unpaired t-test, p = 0.0374 (n = 16 WT sections from 3 mice and 18 G2019S sections from 4 mice)
    • Anxa1 bassoon cluster volume: two-tailed unpaired t-test, p = 0.0148 (n = 16 WT sections from 3 mice and 18 G2019S sections from 4 mice)

    The SIM images are not in the dandiset; they are in the BioImage Archive.

  • BlockedFigure 5I and 5J; Results, LRRK2 disrupts the number and composition of active zone release sites in vulnerable dopamine axons, paragraph 2· Data missing from the datasetdata in BioImage Archive S-BIAD2072 (images); Zenodo doi:10.5281/zenodo.19930567 (per-section values)

    The volume occupied by TH+ fibres in the dorsal striatum does not differ between G2019S and WT mice.

    We found no differences in the volume (Fig. 5I, J, Supplementary Fig. 5C), area, and intensity of TH signal in immunopositive ALDH1A1 fibers (Supplementary Fig. 5D, E) in the dorsal striatum.

    Figure 5I and 5J; Results, LRRK2 disrupts the number and composition of active zone release sites in vulnerable dopamine axons, paragraph 2

    The confocal images are not in the dandiset; they are in the BioImage Archive.

Findings about the data

What attempts found about the dataset itself, for its owner and the archive.

  • Data missingThe Calb1 dF/F in the dandiset is not the trace behind Supplementary Figure 8. None of the 384 published Calb1 triggered traces or evoked integrals match it, no epoch of any power matches a published trace, the transient counts match for 1 of 12 mice, and dF/F recomputed from the deposited raw signal with the published code reproduces the dandiset's series, not the paper's, at any single background fraction. The processing the paper used for Calb1 is neither deposited nor described, so the Calb1 results of the paper cannot be recomputed from the dandiset.
  • Data missingThe dandiset holds only the fiber photometry of Figure 6 and Supplementary Figures 7 and 8. The imaging, proteomics and western blots of Figures 1 to 5 are elsewhere (BioImage Archive, PRIDE, Zenodo), so eight of the paper's main findings cannot be tested on it.
  • OtherThe processed series of mouse 4398 ends 0.8 s after its last onset, a 4 mW stimulation, while the paper's trace for that stimulation is complete and differs from the dandiset's in the samples both hold.
  • Metadata errorThe OptogeneticEpochsTable description gives 8 ms on and 8 ms off for 500 ms, four powers and trains at least 20 s apart. The tables hold eight powers, two kinds of train in Anxa1 files (9 ms pulses every 10 ms for 0.33 s, and 8 ms every 16 ms for 0.51 s), and pairs of trains 15.3 s apart (51% of gaps under 20 s). One train each in mice 4652 and 740 has a pulse length of 0, no period and one pulse.
  • OtherTwo Anxa1 G2019S mice (3742 and 4885) received the paper's four powers as 0.33 s trains of 9 ms pulses, while every other mouse received them as 0.51 s trains of 8 ms pulses. Neither the paper nor the dandiset says so. In these two mice the response does not follow the labelled power (in 3742 the 0.5 mW trains give the smallest response, median 5.7 against 33.5 % dF/F x s at 0.1 mW), so the data cannot confirm their power labels. Leaving the two mice out does not change the Anxa1 result.
  • Metadata errorThe dF/F series (FiberPhotometryResponseSeriesDfOverF) is stated in a.u.; its description and its values are percent dF/F.
  • Metadata errorThe archive's summary of the dandiset lists only a behavioral approach and BehavioralTimeSeries; the files hold fiber photometry and optogenetics.
  • Selection not documentedThe dandiset holds the 27 mice the paper kept after excluding four on histology (one Anxa1 G2019S, one Calb1 G2019S, two Calb1 WT). It does not say that mice were left out or why.
  • Published code disagreeschunking_index.m computes the start of each window as trigger - fs*ti, so with ti = -1 the window used for the evoked integral and for the spontaneous exclusion starts 1 s after onset. The source data show that the figures used the intended window starting 1 s before onset; the code as published gives the reverse sign.
  • Published code disagreesplot_results.m selects power code 'h' for Figure 6E, which the lab's stimulation key, as used by the conversion, maps to 4 mW; the figure, its legend and the source data are at 0.5 mW.
  • Published code disagreesThe Methods and transient_by_threshold.m give the integral of dF/F over each spontaneous transient; the published values of Figure 6F and Supplementary Figure 8C are 0.005 times the mean dF/F over each transient, a duration-normalized integral. The code that computes them is not in the repository.
  • Paper inconsistentFor the per-mouse comparisons the Methods and the asterisks name Welch's test, the legends give one-tailed two-sample t-test p-values, and the code runs a two-tailed Student test. The Figure 6F count of 6 of 8 follows the one-tailed Student test; Welch's test gives 7.
  • OtherThe paper does not cite the dandiset; its data statement names Zenodo, PRIDE and the BioImage Archive.

Notebooks

Every registered entry that uses this dataset. An entry can hold several notebooks, and can use more than one dataset.

Reproduction LRRK2-G2019S and dopamine release from Anxa1+ and Calb1+ neurons (Chen, He et al. 2026)

Tests the findings of Chen, He et al. (2026). On dandiset 001933, which holds GRAB-DA3m fiber photometry in the dorsal striatum during optogenetic stimulation of Anxa1+ (15 mice) or Calb1+ (12 mice) SNc dopamine neurons in LRRK2-WT and LRRK2-G2019S mice, it compares evoked and spontaneous dopamine release between genotypes, per power and per mouse, and links the dandiset to the paper's published source data. The imaging, proteomics and western blots of Figures 1 to 5 are not in the dandiset; their claims are tested on the data the paper deposited on Zenodo, in PRIDE and in the BioImage Archive, and counted apart. All files

Verification

  • Round 1
    2026-10-15    Agreed with 18 of 18 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: The first executed notebook (commit 6a2acb7) with the conclusion cells and the summary removed, the helper module and the claims file, with the paper's main text. The verifier listed the version's assets through the DANDI API and ran synthetic checks of double_threshold, _movmean, evoked_integrals, spontaneous_transients, cohens_d and one_tailed_less.
  • Round 2
    2026-10-15    Agreed with 18 of 18 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: The full re-executed notebook of the first revision (commit 0c6b642) with its conclusions and summary, the README, the attempt record, the helper module and the claims file. The verifier checked every Result paragraph and the summary against the printed outputs and recomputed 131.9 and 302.9 from the per-mouse table. It did not read the Supplementary Figure 7 and 8 legends.

Method differences

How the tests differed from the paper’s method or data, and the claims each applies to.

  • Run on the dandiset's Calb1 dF/F, which differs from the trace behind Supplementary Figure 8.supp8c-calb1-spontaneous-not-reduced supp8e-calb1-evoked-reduced supp8e-calb1-few-mice-reduced cohens-d-anxa1-larger
  • The criterion fixed the integral of each spontaneous transient; the published values turned out to be the mean dF/F over the transient. The mean is shown as a variant and does not change the outcome.source-data-link
  • The integral is over each train's light-on period, as the Methods state; the paper's values come from the code's window, -0.1 to 1.0 s, shown as a variant. The baseline, which the Methods do not give, is the code's.fig6e-anxa1-evoked-reduced
  • The paper's plotting code selects power code 'h' for this panel; the panel is tested at the 0.5 mW of the legend, which the source data confirm, and 4 mW is shown as a variant.fig6e-anxa1-evoked-reduced
  • The Methods name Welch's test, the legend's p-values are one-tailed and the code runs a two-tailed Student test; all four readings are shown and all give 7.fig6e-anxa1-evoked-per-mouse
  • In the code's window variant, 55 WT stimulations at 4 mW in place of 56, as one falls at the end of a truncated series.supp7c-anxa1-evoked-all-powers
  • The integral of each transient is used, as the Methods state; the paper's values are 0.005 times the mean dF/F over the transient, shown as a variant.fig6f-anxa1-spontaneous-reduced
  • The integral of each transient is used, as the Methods state; the paper's measure is shown as a variant.fig6f-anxa1-spontaneous-per-mouse
  • The legend does not state the power of the per-mouse panel; 0.5 mW was fixed before the analysis and the other powers are shown.supp8e-calb1-few-mice-reduced

Provenance

Attempt record
001933-chen-2026-01
Paper
Leucine-rich repeat kinase 2 impairs the release sites of Parkinson’s disease vulnerable dopamine axons
Date
2026-10-15
Made by
An agent, run by CatalystNeuro
Dataset
DANDI:001933
Version
0.260825.1457 (doi:10.48324/dandi.001933/0.260825.1457)
Run on
GitHub Actions
Harness
Claude Code (GitHub Actions)
Model
claude-opus-5-5
Protocol
pilot-6

Transcripts of the agent runs

Each run’s prompt, messages and tool calls, with long output cut and the text of the paper left out, and its final report.

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