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DANDI:001528

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Fiber photometry of SNc/SNr dopamine and GABA neuron responses to optogenetic STN and PPN stimulation in Parkinson's disease

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  • 12 reproduced
  • 5 partially reproduced
  • 3 not reproduced
  • 5 blocked

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Claims

From the paper Parkinson’s Disease-vulnerable and -resilient dopamine neurons display opposite responses to excitatory input

Reproducing Hadjas et al. (2025) from dandiset 001528 21

Notebook reproduce_hadjas_2025.ipynb

  • Not reproducedLegends of Figures 2 to 5, S3 and S4

    The number of mice per experimental group is as given in the figure legends; SNr GABA neurons STN 7 and PPN 8 (Figure 2); SNc pan-DA neurons STN 11 and PPN 9 (Figure 3); GRAB-DA in TS and DLS, STN 6 and 7, PPN 9 and 9 (Figure 4); DA terminals in TS and DLS with STN stimulation, 9 and 9 (Figure S3); Vglut2+ DA neurons STN 10 and PPN 10, Anxa1+ terminals in DLS STN 8 and PPN 10 (Figure 5); Anxa1+ cell bodies in SNc STN 5 and PPN 4 (Figure S4).

    Not quoted: Counts gathered from the legends of Figures 2 to 5, S3 and S4; no single sentence states them.

    10 of 16 counts match. SNr GABA, pan-DA and GRAB-DA groups match exactly, as do DA terminals in TS and Vglut2 with PPN. DA terminals in DLS have 8 mice (paper 9) and Vglut2 with STN 9 (paper 10). The Anxa1 groups have DLS recordings for 5 (STN) and 4 (PPN) mice against the paper's 8 and 10, and SNc recordings for 8 and 10 against 5 and 4. All four Anxa1 counts would match if the nine recordings without a site suffix were DLS recordings; their signals resemble the SNc recordings, and the paper's cell-body statistics are matched by the dual mice's SNc recordings alone, so the DLS recordings of those nine mice appear to be missing. For Vglut2 STN the paper's own Wilcoxon statistics fit 9 mice (W = 41, 43, -5 give exact p = 0.0117, 0.0078, 0.82 with n = 9, the paper's values, and 0.037, 0.027, 0.85 with n = 10), so the legend's 10 is likely an error; counted that way 11 of 16 match, still below 12.

    How the test differed from the paper’s method

    • Counted from the durations protocol; the frequencies protocol gives the same counts.
  • Not reproducedResults, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 3; Figure 3F and 3G

    PPN stimulation also evokes SNc pan-DA responses that vary with train duration (Friedman test, F = 11.5, p = 0.009).

    Stimulation of PPN inputs led to similarly variable and dynamic DA responses... (Varying durations: Friedman’s test, F=11.5, p=0.009

    Results, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 3; Figure 3F and 3G

    What the paper reports

    • Friedman’s test, F=11.5, p = 0.009

    Means during 0.25, 1 and 4 s PPN trains are -0.60, 1.03 and 0.70 %, n = 9. Friedman p = 0.26, 0.25 and 0.46 under readings (a) to (c), where the paper reports F = 11.5, p = 0.009. Without the three PPN recordings whose clock could not be shown from the response (C3164, C5007, C5008), n = 6, readings (a) and (b) give p = 0.11 and 0.14.

    How the test differed from the paper’s method

    • The paper's measure for this comparison is not stated; the mean during the train (and the area under the curve) were used, as for the STN comparison, which matches the paper there.
  • Not reproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4E and 4H; Figure S3F and S3L

    Low-frequency (5 Hz) stimulation of either STN or PPN increases DLS dopamine.

    Notably, low-frequency (i.e. 5 Hz) optogenetic stimulation of either the STN or PPN increased DLS dopamine levels

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4E and 4H; Figure S3F and S3L

    1 s trains at 5 Hz (Figure 4E and 4H), mean GRAB-DA in DLS during the train, STN 1.51 % (4 of 7 above 0, p = 0.22), PPN 1.40 % (6 of 9, p = 0.13). The sentence also cites Figure S3F and S3L, the 4 s DLS panels; for 4 s trains, a variant, STN 5.41 % (7 of 7, p = 0.00062) and PPN 2.01 % (6 of 9, p = 0.07), one input of two, which would be partially reproduced under that reading. The 1 s after offset is positive in all six conditions (0.96 to 6.76 %).

    How the test differed from the paper’s method

    • The paper does not state the window or test for this observation; the mean during 1 s trains (Figure 4E and 4H) against 0 was fixed in the criterion. The sentence cites both the 1 s panels and the 4 s panels (Figure S3F and S3L), and its account of summation over pulses fits longer trains; under the 4 s reading the effect holds for STN only.
  • Partially reproducedResults, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3B

    A 250 ms 40 Hz train of STN inputs elicits a net increase in SNc pan-DA neuron activity that peaks after stimulus offset (latency to peak 0.50 +/- 0.03 s, mean +/- SEM).

    a brief (250 ms) 40 Hz train of STN inputs elicited a net increase in DA neuron activity that peaked after stimulus offset (Figure 3B; latency to peak, 0.50 +/− 0.03 s).

    Results, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3B

    With the window fixed in the criterion (peak from onset to 2.25 s) the mean latency is 0.786 s, SEM 0.204, n = 11, outside 0.50 +/- 0.03 s, because two mice peak at 2.03 and 2.24 s. Ten of 11 mice peak after offset and the net response over 0 to 1.25 s is positive (2.89 %, t = 3.28, p = 0.0083). With a window ending at 1.25 s, a variant, the mean latency is 0.492 s, SEM 0.033, the paper's value. The two late-peaking mice (C4217, B8612) have small responses, an early local maximum at 0.41 and 0.62 s, and a slow rise that continues past the window (maximum over 0 to 5 s at 2.97 and 2.78 s), which looks like a late rebound or drift.

    How the test differed from the paper’s method

    • The paper does not give the window in which the peak is sought; the criterion fixed 0 to 2.25 s, and the variant 0 to 1.25 s matches the paper.
  • Partially reproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4C and 4F

    In DLS the DA inhibition is followed by a post-stimulus rebound above baseline.

    The DA inhibition was sustained for the duration of the stimulus and was followed by a post-stimulus rebound increase in evoked DA above baseline (Figure 4C, F).

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4C and 4F

    After 1 s 40 Hz trains, PPN 4.53 % (8 of 9 above 0, p = 0.017), STN 0.87 % (5 of 7, p = 0.29). After 0.25 and 4 s trains the rebound is significant for both inputs (p 0.0039 to 0.015).

    How the test differed from the paper’s method

    • The rebound window (1 s after offset) and test are choices; the paper gives no statistic.
  • Partially reproducedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5N, 5O, 5S and 5T

    The Anxa1+ terminal inhibition scales with frequency (STN, 0.25 s F = 18.0, 1 s F = 15.5, 4 s F = 15.3; PPN, 0.25 s F = 11.5, 1 s F2,15 = 11.0, 4 s F2,18 = 7.2).

    The inhibition again scaled with frequency for shorter-duration STN stimulation and all durations tested for PPN

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5N, 5O, 5S and 5T

    What the paper reports

    • STN, 0.25 s: Friedman’s test, F=18.0, p = 3 × 10⁻⁴
    • STN, 1 s: Friedman’s test, F=15.5, p = 0.015
    • STN, 4 s: Friedman’s test, F=15.3, p = 0.001
    • PPN, 0.25 s: Friedman’s test, F=11.5, p = 2 × 10⁻⁴
    • PPN, 1 s: one-way repeated-measures ANOVA, F2,15=11.0, p = 0.006
    • PPN, 4 s: one-way repeated-measures ANOVA, F2,18=7.2, p = 0.002

    With the dandiset's DLS recordings (5 STN, 4 PPN mice) 5 of 6 tests hold (p 0.0043 to 0.026, 40 Hz below 5 Hz); PPN 4 s does not (F = 1.95, p = 0.24). With the unsuffixed recordings added, 3 of 6 hold. The paper's F2,15 and F2,18 for PPN 1 and 4 s imply about 8.5 and 10 mice (6.8 to 13.3 with the dfs rounded), against 4 here, so the samples are smaller than the paper's for the reason given under fig5-anxa1-dls-inhibited.

    How the test differed from the paper’s method

    • 5 and 4 mice, where the paper has 8 and 10 (see fig5-anxa1-dls-inhibited).
  • Partially reproducedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5L and 5Q

    Anxa1+ terminals in DLS show a transient increase in activity at stimulus offset, for both inputs.

    In DLS terminals from SNc Anxa1+ neurons, stimulation of both STN and PPN inputs produced inhibition followed by apparent rebound at stimulus offset

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5L and 5Q

    After 1 s trains, STN 1.02 % (5 of 5 above 0, p = 0.0044), PPN 0.57 % (3 of 4, p = 0.14). The 0.25 and 4 s trains give the same picture (STN p = 0.036 and 0.026, PPN p = 0.20 and 0.11).

    How the test differed from the paper’s method

    • 5 and 4 mice, where the paper has 8 and 10.
    • The rebound window (1 s after offset) and test are choices; the paper gives no statistic.
  • Partially reproducedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure S4C and S4F

    Anxa1+ SNc cell bodies show stimulation-induced inhibition (paired t-test, STN 0.25 s t = 3.1, 1 s t = 4.0, 4 s t = 7.2, n = 5; PPN t = 4.8, 8.4, 3.3, n = 4) followed by post-stimulus rebound activation.

    analysis of that subset revealed the same pattern of responses including stimulation-induced inhibition of activity... followed by post-stimulus rebound activation (Figure S4C, F).

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure S4C and S4F

    What the paper reports

    • STN, 0.25 s: paired t-test, t=3.1, p = 0.035 (n = 5 mice)
    • STN, 1 s: paired t-test, t=4.0, p = 0.016 (n = 5 mice)
    • STN, 4 s: paired t-test, t=7.2, p = 0.002 (n = 5 mice)
    • PPN, 0.25 s: paired t-test, t=4.8, p = 0.018 (n = 4 mice)
    • PPN, 1 s: paired t-test, t=8.4, p = 0.004 (n = 4 mice)
    • PPN, 4 s: paired t-test, t=3.3, p = 0.044 (n = 4 mice)

    With all SNc-labelled recordings (8 STN, 10 PPN mice) 5 of 6 tests show a significant decrease (p 0.0003 to 0.014); STN 0.25 s does not (t = -1.56, p = 0.16). Restricted to the mice with both a DLS and an SNc file (5 and 4, the paper's n), a variant, all 6 are significant with the paper's statistics (t = 3.13, 3.98, 7.26, 4.72, 8.35, 3.33 against 3.1, 4.0, 7.2, 4.8, 8.4, 3.3). The statement's post-stimulus rebound is not seen in the cell bodies after 1 s trains (STN -0.08 %, PPN 0.03 %, p = 0.65 and 0.80; dual mice p = 0.53 and 0.16).

    How the test differed from the paper’s method

    • The dandiset labels 8 and 10 mice as SNc where the paper analysed 5 and 4; the outcome uses the dandiset's labels as fixed in the criterion.
  • ReproducedResults, STN and PPN activation increase SNr GABA neuron activity in vivo, paragraph 3; Figure 2B and 2E with insets

    Optogenetic stimulation of STN or PPN inputs increases SNr GABA neuron activity (paired t-test on the 1 s train, STN t = 3.8, p = 0.008; PPN t = 9.2, p < 0.0001).

    Optogenetic stimulation of either STN or PPN led to a significant increase in SNr GABA neuron activity (paired t-test, STN: t=3.8, p=0.008; PPN: t=9.2, p<0.0001)

    Results, STN and PPN activation increase SNr GABA neuron activity in vivo, paragraph 3; Figure 2B and 2E with insets

    What the paper reports

    • STN: paired t-test, t=3.8, p = 0.008
    • PPN: paired t-test, t=9.2, p < 10⁻⁴

    1 s 40 Hz trains, mean during the train against the 1 s before onset. STN mean 18.89 % dF/F, paired t = 3.86, p = 0.0083, n = 7 (paper t = 3.8, p = 0.008); PPN 6.45 %, t = 9.19, p = 3.7e-05, n = 8 (paper t = 9.2). The 0.25 and 4 s trains also give significant increases (p 1.4e-05 to 0.0066).

    How the test differed from the paper’s method

    • The response window (mean during the train) and pre-stimulus window (same length, before onset) are choices; the paper does not state them.
    • All seven STN mice have 10 trials per condition, where the Methods state 5.
  • ReproducedResults, STN and PPN activation increase SNr GABA neuron activity in vivo, paragraph 3; Figure 2C and 2F

    The SNr GABA response scales with stimulation frequency from 5 to 40 Hz (Friedman test on 1 s trains, STN F = 21.0, p = 0.0001; PPN F = 18.2, p = 0.0004).

    the amplitude of the response scaled with the frequency, increasing from 5 to 40 Hz (Friedman’s test, STN: F=21.0, p=0.0001; PPN: F=18.2, p=0.0004)

    Results, STN and PPN activation increase SNr GABA neuron activity in vivo, paragraph 3; Figure 2C and 2F

    What the paper reports

    • STN: Friedman’s test, F=21.0, p = 10⁻⁴
    • PPN: Friedman’s test, F=18.2, p = 4 × 10⁻⁴

    1 s trains of the frequencies protocol. STN means rise from 4.07 to 32.66 % between 5 and 40 Hz, Friedman 21.00, p = 0.00011, 7 of 7 mice higher at 40 than 5 Hz; PPN 1.57 to 6.10 %, Friedman 18.15, p = 0.00041, 8 of 8 (paper 21.0 and 18.2). A repeated-measures ANOVA variant gives p = 0.014 and 0.0001.

    How the test differed from the paper’s method

    • The conversion code names the STN 1 s block of these mice as 10 mW, while the files and the Methods give 5 mW; the analysis takes the files as they are.
  • ReproducedResults, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3B and 3C

    For SNc pan-DA neurons the STN-evoked response varies with train duration; with 1 and 4 s trains an initial increase is followed by inhibition (Friedman test, F = 13.0, p = 0.005).

    When the train was extended to 1 or 4 s, we observed an initial increase in activity followed by inhibition (Friedman’s test, F=13.0, p=0.005)

    Results, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3B and 3C

    What the paper reports

    • Friedman’s test, F=13.0, p = 0.005

    Means during 0.25, 1 and 4 s trains are 0.52, 0.97 and -3.13 %, n = 11. Reading (a), Friedman over three durations, 13.64, p = 0.0011; reading (b), with the pre-stimulus window as a fourth group, 12.93, p = 0.0048, matching the paper's F = 13.0, p = 0.005; reading (c), area under the curve, p = 0.06. In 4 s trains the first 0.5 s (0.71 %) is above the last 1 s (-5.05 %) in all 11 mice, paired t = 4.81, p = 0.00071.

    How the test differed from the paper’s method

    • The paper's F and p fit four groups while three durations were tested; readings (a) and (b) match, and (b) gives the paper's value.
  • ReproducedResults, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3D

    The amplitude of the SNc pan-DA response during STN stimulation does not scale with frequency (Friedman test, F = 4.2, p = 0.24).

    the amplitude of the responses evoked during stimulation did not scale neatly with frequency (Friedman’s test, F=4.2, p=0.24) (Figure 3D).

    Results, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 2; Figure 3D

    What the paper reports

    • Friedman’s test, F=4.2, p = 0.24

    1 s trains, Friedman 4.20, p = 0.24, n = 11 (paper F = 4.2, p = 0.24); 40 minus 5 Hz 0.21 % dF/F. Variants with 0.25 s (p = 0.31) and 4 s trains (p = 0.18, 5 mice with all four frequencies) also find no effect.

    How the test differed from the paper’s method

    • The paper does not say which train duration Figure 3D shows; the 1 s train was fixed in the criterion.
  • ReproducedResults, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 3; Figure 3H

    The SNc pan-DA response to PPN stimulation does not vary with frequency (repeated-measures one-way ANOVA, F2,15 = 1.35, p = 0.28).

    Stimulation of PPN inputs led to similarly variable and dynamic DA responses... Varying frequencies: RM one-way ANOVA, F2,15=1.35, p=0.28)

    Results, STN and PPN activation drive multiphasic responses in DA neurons, paragraph 3; Figure 3H

    What the paper reports

    • RM one-way ANOVA, F2,15=1.35, p = 0.28

    1 s trains, repeated-measures ANOVA F = 1.35 on Greenhouse-Geisser corrected df 1.85 and 14.8, p = 0.29, n = 9 (paper F2,15 = 1.35, p = 0.28); 40 minus 5 Hz 1.30 %. Variants with 0.25 and 4 s trains give p = 0.83 and 0.32.

    How the test differed from the paper’s method

    • The 1 s train was fixed in the criterion, as the paper does not name the duration.
  • ReproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 2; Figure 4C and 4F

    STN or PPN stimulation evokes opposite DA release in TS (increase) and DLS (decrease) (two-way ANOVA, striatal site, STN F1,11 = 40.9, PPN F1,16 = 36.4, p < 0.0001; site by time interaction of the same size).

    Stimulation of STN or PPN inputs to SNc evoked strikingly opposite DA responses in TS and DLS

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 2; Figure 4C and 4F

    What the paper reports

    • STN, striatal site: 2-way ANOVA, F1,11=40.9, p < 10⁻⁴
    • STN, striatal site by time interaction: 2-way ANOVA, F1,11=40.8, p < 10⁻⁴
    • PPN, striatal site: 2-way ANOVA, F1,16=36.4, p < 10⁻⁴
    • PPN, striatal site by time interaction: 2-way ANOVA, F1,16 =36.4, p < 10⁻⁴

    GRAB-DA, 1 s 40 Hz trains. STN, TS 12.45 % (6 of 6 above 0), DLS -8.91 % (7 of 7 below 0), site by time interaction F(1, 11) = 40.9, p = 5.1e-05; PPN, TS 11.39 % (9 of 9), DLS -5.75 % (9 of 9), F(1, 16) = 36.4, p = 1.7e-05, the paper's values. The 0.25 and 4 s trains give the same pattern.

  • ReproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 2; Figure 4D and 4G; Figure S3C, S3D, S3I and S3J

    In TS, the DA increase evoked by either input scales with frequency, for all train durations (STN, repeated-measures ANOVA, 0.25 s F2,8 = 7.5, 1 s F2,7 = 13.6, 4 s F2,9 = 16.9; PPN, Friedman, F = 20.0, 24.0, 23.2).

    In TS, stimulation of either input elicited an increase in DA release that scaled with frequency... and was observed for all train durations

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 2; Figure 4D and 4G; Figure S3C, S3D, S3I and S3J

    What the paper reports

    • STN, 0.25 s: one-way repeated-measures ANOVA, F2,8=7.5, p = 0.02
    • STN, 1 s: one-way repeated-measures ANOVA, F2,7=13.6, p = 0.004
    • STN, 4 s: one-way repeated-measures ANOVA, F2,9=16.9, p = 0.001
    • PPN, 0.25 s: Friedman’s test, F=20.0, p = 2 × 10⁻⁴
    • PPN, 1 s: Friedman’s test, F=24.0, p < 10⁻⁴
    • PPN, 4 s: Friedman’s test, F=23.2, p < 10⁻⁴

    All six tests hold, with the 40 Hz mean above the 5 Hz mean. STN repeated-measures ANOVA F = 7.62, 13.76, 17.31 for 0.25, 1 and 4 s (p = 0.019, 0.0044, 0.0011; paper 7.5, 13.6, 16.9); PPN Friedman 19.80, 24.33, 23.27 (p at most 0.0002; paper 20.0, 24.0, 23.2).

  • ReproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4E and 4H; Figure S3E, S3F, S3K and S3L

    In DLS, the DA inhibition scales with frequency and is most prominent at higher frequencies (STN, repeated-measures ANOVA, 0.25 s F = 7.5, 1 s F = 12.8, 4 s F = 46.8; PPN, 0.25 s Friedman F = 12.3, 1 s and 4 s repeated-measures ANOVA F = 12.8 and 10.2).

    The inhibition in DA scaled with frequency and was most prominent at higher frequencies

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 3; Figure 4E and 4H; Figure S3E, S3F, S3K and S3L

    What the paper reports

    • STN, 0.25 s: one-way repeated-measures ANOVA, F2,9=7.5, p = 0.015
    • STN, 1 s: one-way repeated-measures ANOVA, F1,11=12.8, p = 5 × 10⁻⁴
    • STN, 4 s: one-way repeated-measures ANOVA, F2,13=46.8, p < 10⁻⁴
    • PPN, 0.25 s: Friedman’s test, F=12.3, p = 0.006
    • PPN, 1 s: one-way repeated-measures ANOVA, F1,11=12.8, p = 0.002
    • PPN, 4 s: one-way repeated-measures ANOVA, F2,13=10.2, p = 0.004

    All six tests hold, with the 40 Hz mean below the 5 Hz mean (p below 0.0001 to 0.013). STN 0.25 and 4 s F = 7.89 and 47.23 (paper 7.5, 46.8); PPN 0.25 s Friedman 11.53 (paper 12.3), PPN 1 and 4 s F = 12.98 and 15.92 (paper 12.8, 10.2). STN 1 s gives F = 26.17 where the paper gives F1,11 = 12.8, p = 0.0005, the same F and df it gives for PPN 1 s.

  • ReproducedResults, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 4; Figure S3N and S3O

    Calcium in DA terminals in TS and DLS shows opposite responses to STN stimulation, as the GRAB-DA recordings do.

    Consistent with the GRABDA recordings, calcium responses in DA terminals in TS and DLS showed opposite patterns of activity in response to STN stimulation (Figure S3N-O).

    Results, STN and PPN inputs evoke opposite patterns of DA release in striatal subregions, paragraph 4; Figure S3N and S3O

    DA terminal GCaMP, 1 s trains, TS 8.96 % (9 of 9 above 0), DLS -4.41 % (7 of 8 below 0), site by time interaction F(1, 15) = 26.2, p = 0.00013. The DLS terminals rebound after offset (6.73 %, 8 of 8 above 0).

    How the test differed from the paper’s method

    • 8 DLS mice, where the paper has 9.
  • ReproducedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 2; Figure 5B, 5C, 5G and 5H; Figure S4A and S4D

    Stimulation of STN or PPN inputs increases the activity of Vglut2+ DA neurons in SNc (STN, Wilcoxon, 0.25 s W = 41, p = 0.012, 1 s W = 43, p = 0.008, 4 s W = -5, p = 0.82; PPN, paired t-test, 0.25 s t = 2.9, p = 0.02, 1 s t = 3.4, p = 0.008, 4 s t = 3.0, p = 0.01).

    Stimulation of either STN or PPN inputs evoked an increase in the activity of Vglut2+ DA neurons in SNc

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 2; Figure 5B, 5C, 5G and 5H; Figure S4A and S4D

    What the paper reports

    • STN, 0.25 s: Wilcoxon’s test, W=41.0, p = 0.012
    • STN, 1 s: Wilcoxon’s test, W=43.0, p = 0.008
    • STN, 4 s: Wilcoxon’s test, W=-5.0, p = 0.82
    • PPN, 0.25 s: paired t-test, t=2.9, p = 0.02
    • PPN, 1 s: paired t-test, t=3.4, p = 0.008
    • PPN, 4 s: paired t-test, t=3.0, p = 0.01

    STN Wilcoxon W = 43 and 43 for 0.25 and 1 s (p = 0.0078 each, n = 9; paper 41 and 43); PPN paired t = 2.89 and 3.42 (p = 0.018 and 0.0076, n = 10; paper 2.9 and 3.4). For 4 s trains STN W = -5, p = 0.82 as in the paper, and PPN t = 2.56, p = 0.031 (paper 3.0, p = 0.01).

    How the test differed from the paper’s method

    • 9 STN mice, where the legend gives 10; the paper's W and p values are the exact values for 9 mice.
  • ReproducedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 2; Figure 5D, 5E, 5I and 5J

    The Vglut2+ DA neuron increase scales with frequency for short STN trains and for all PPN durations (Friedman, STN 0.25 s F = 15.5, p = 0.001, 1 s F = 5.9, p = 0.11, 4 s F = 7.0, p = 0.07; PPN F = 18.8, 24.8, 20.2, p <= 0.0003).

    increases in activity scaled with frequency for short-duration STN stimulations and all durations tested for PPN

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 2; Figure 5D, 5E, 5I and 5J

    What the paper reports

    • STN, 0.25 s: Friedman’s test, F=15.5, p = 0.001
    • STN, 1 s: Friedman’s test, F=5.9, p = 0.11
    • STN, 4 s: Friedman’s test, F=7.0, p = 0.07
    • PPN, 0.25 s: Friedman’s test, F=18.8, p = 3 × 10⁻⁴
    • PPN, 1 s: Friedman’s test, F=24.8, p < 10⁻⁴
    • PPN, 4 s: Friedman’s test, F=20.2, p = 10⁻⁴

    STN 0.25 s Friedman 13.53, p = 0.0036; PPN 0.25, 1 and 4 s 11.23, 17.91, 16.20 (p = 0.011, 0.0005, 0.0010), all with the 40 Hz mean above the 5 Hz mean. STN 1 and 4 s are not significant (p = 0.43 and 0.16), as in the paper (0.11 and 0.07).

    How the test differed from the paper’s method

    • The PPN tests use the 7 of 10 mice that have all four frequencies; C3412, C3798 and C4707 have no 5 Hz trains in the dandiset. The paper's PPN 1 s Friedman statistic of 24.8 needs at least 9 mice (the maximum is 3n), so the paper had 5 Hz trains that are not deposited.
  • ReproducedTitle; Abstract; Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5

    Excitatory inputs from STN and PPN activate PD-resilient Vglut2+ DA neurons but inhibit PD-vulnerable Anxa1+ DA neurons.

    excitatory inputs from STN and PPN led to activation of PD-resilient Vglut2+ DA neurons but inhibition of PD-vulnerable Anxa1+ DA neurons.

    Title; Abstract; Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5

    1 s 40 Hz trains. STN, Vglut2 6.54 % against Anxa1 DLS -1.73 % (Welch t = 3.56, p = 0.0066); PPN 9.35 % against -1.48 % (t = 3.90, p = 0.0032). It holds with the unsuffixed Anxa1 recordings added to DLS (p = 0.0097 and 0.005) and against the Anxa1 SNc recordings (p = 0.017 and 0.0065).

    How the test differed from the paper’s method

    • Anxa1 DLS recordings of 5 and 4 mice, where the paper has 8 and 10.
  • BlockedResults, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5L, 5M, 5Q and 5R; Figure S4B and S4E· Data missing from the datasetverifier disagreed at first

    In DLS terminals of SNc Anxa1+ neurons, STN and PPN stimulation produce inhibition (STN, 0.25 s t = 6.4, p = 0.0004, 1 s W = -36, p = 0.005, 4 s W = -36, p = 0.008; PPN, 0.25 s t = 3.9, p = 0.004, 1 s W = -55, p = 0.002, 4 s t = 3.8, p = 0.004).

    In DLS terminals from SNc Anxa1+ neurons, stimulation of both STN and PPN inputs produced inhibition followed by apparent rebound at stimulus offset

    Results, Excitatory input from STN and PPN evoke opposite responses in PD-vulnerable and PD-resilient DA subtypes, paragraph 3; Figure 5L, 5M, 5Q and 5R; Figure S4B and S4E

    What the paper reports

    • STN, 0.25 s: paired t-test, t=6.4, p = 4 × 10⁻⁴
    • STN, 1 s: Wilcoxon’s test, W=-36.0, p = 0.005
    • STN, 4 s: Wilcoxon’s test, W=-36.0, p = 0.008
    • PPN, 0.25 s: paired t-test, t=3.9, p = 0.004
    • PPN, 1 s: Wilcoxon’s test, W=-55.0, p = 0.002
    • PPN, 4 s: paired t-test, t=3.8, p = 0.004

    The dandiset holds Anxa1 DLS recordings for 5 (STN) and 4 (PPN) mice where the paper has 8 and 10. At these numbers the Wilcoxon tests the paper uses for three of the six conditions cannot reach p < 0.05 (smallest p 0.0625 and 0.125), so reproduced (6 of 6) cannot be reached with the deposited mice. The three t-tests can reach it, so partially reproduced (3 to 5 of 6) was reachable and was not reached; 2 of 6 tests are significant (STN 0.25 s t = -6.14, p = 0.0036; PPN 0.25 s t = -3.46, p = 0.041; PPN 4 s p = 0.13). No STN mouse goes up in any condition, and one PPN mouse in 4 s trains. With the nine recordings without a site suffix added to DLS, a variant, all 6 tests are significant. Its STN 4 s W = -36 (p = 0.0078) is the paper's, but the other two W (-34 and -51 against -36 and -55) and the t values (2.65, 2.47, 2.98 against 6.4, 3.9, 3.8) differ, while the cell-body statistics match closely with the dual mice (p to two digits, t within 0.08). The paper's statistics fix its n; W = -36 and -55 equal -n(n+1)/2 for n = 8 and 10, and t = 6.4 with p = 0.0004 needs 7 df (4 df give p = 0.0031). The DLS recordings of nine of the paper's mice are not in the dandiset.

Not tested in a notebook 4

4 data missing from the dataset
  • BlockedResults, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure 1D and 1E· Data missing from the dataset

    In human SNc, TH+ neurons (Mann-Whitney U = 2.0, p = 0.002) and TH+/ANXA1+ neurons (U = 1.0, p < 0.0001) are fewer in PD cases (n = 7) than in controls (n = 12).

    the total number of TH-expressing neurons was significantly decreased in PD cases compared to controls (Mann-Whitney’s test, U=2.0, p=0.002) (Figure 1D). The number of ANXA1+ DA neurons was also significantly reduced in PD cases (U=1.0, p<0.0001)

    Results, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure 1D and 1E

    What the paper reports

    • TH+ neurons: Mann-Whitney’s test, U=2.0, p = 0.002 (n = 7 PD cases and 12 controls)
    • TH+/ANXA1+ neurons: Mann-Whitney’s test, U=1.0, p < 10⁻⁴ (n = 7 PD cases and 12 controls)

    The human RNAscope counts are not in the dandiset, which holds mouse photometry only. The preprint has no data availability statement, and the dandiset metadata and the conversion repository link no other deposit.

  • BlockedResults, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure 1F· Data missing from the dataset

    Among remaining DA neurons in PD, ANXA1+ neurons are de-enriched to 10 +/- 7% of control, ALDH1A1+ to 41 +/- 12%, while CALB1+ neurons trend toward enrichment (301 +/- 103%).

    a trend toward enrichment of CALB1+ DA neurons (301 +/− 103 %control, unpaired t-test, t=1.9, p=0.10) compared to the significant de-enrichment observed for ALDHA1A1+ DA neurons (41 +/− 12 %control, t=4.9, p=0.002), and especially ANXA1+ DA neurons

    Results, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure 1F

    What the paper reports

    • CALB1+ fraction, PD against control: unpaired t-test, t=1.9, p = 0.1
    • ALDH1A1+ fraction, PD against control: unpaired t-test, t=4.9, p = 0.002
    • ANXA1+ fraction, PD against control: Mann-Whitney, U=3.0, p = 3 × 10⁻⁴

    Human tissue counts are not in the dandiset nor in any deposit the paper or the dandiset names (see fig1de-th-anxa1-reduced).

  • BlockedResults, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure S1B to S1F· Data missing from the dataset

    TH+/CALB1+ neuron counts are not significantly changed in PD (U = 19.5, p = 0.08) while TH+/ALDH1A1+ counts are reduced (U = 1.0, p < 0.0001).

    the number of CALB1+ DA neurons was not significantly affected, though a trend was observed (U=19.5, p=0.08) (Figure S1B-C), while ALDH1A1+ DA neurons were significantly reduced in PD (U=1.0, p<0.0001)

    Results, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 2; Figure S1B to S1F

    What the paper reports

    • TH+/CALB1+ neurons: Mann-Whitney’s test, U=19.5, p = 0.08
    • TH+/ALDH1A1+ neurons: Mann-Whitney’s test, U=1.0, p < 10⁻⁴

    Human tissue counts are not in the dandiset nor in any deposit the paper or the dandiset names (see fig1de-th-anxa1-reduced).

  • BlockedResults, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 1; Figure S1G to S1J· Data missing from the dataset

    Immunofluorescence confirms fewer TH+ and TH+/ALDH1A1+ neurons and a lower fraction of TH+ neurons expressing ALDH1A1 in PD (n = 11) than in controls (n = 15), and counts agree with RNAscope in four cases processed both ways.

    Quantification of IF showing significant decrease in TH+, TH+/ALDH1A1+, and % TH+/ALDH1A1+ showing de-enrichment in PD (n=11) relative to control (n=15).

    Results, ANXA1 is expressed in human SNc and marks a PD-vulnerable DA subtype, paragraph 1; Figure S1G to S1J

    Human immunofluorescence counts are not in the dandiset nor in any deposit the paper or the dandiset names (see fig1de-th-anxa1-reduced).

Findings about the data

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

  • Data missingFor the Anxa1 mice the dandiset holds DLS terminal recordings for 5 (STN) and 4 (PPN) mice where the paper analyses 8 and 10. Nine mice (C5903, C5906, C5992, C6900, C6902, C7244, C7245, C7248, C7249) have only recordings labelled SNc, without a site suffix in the file name. Their signals resemble SNc recordings, and the paper's cell-body statistics are reproduced closely by the other nine mice's SNc recordings (p to two digits, t within 0.08), so the DLS recordings of these nine mice appear not to be deposited, and the nine SNc recordings were not used in the paper.
  • Selection not documentedThe dandiset includes Anxa1 SNc recordings from nine mice that the paper's cell-body analysis (n = 5 and 4) leaves out, and it does not say which recordings the paper used.
  • Data missingThe human RNAscope and immunofluorescence counts of Figure 1 and Figure S1 and the histology of Figure S2 are not in the dandiset, and the preprint has no data availability statement.
  • Data missingDA terminals in DLS have 8 mice where Figure S3 gives 9.
  • Paper inconsistentThe Figure 5 legend gives 10 mice for Vglut2+ neurons with STN stimulation, while the paper's Wilcoxon statistics (W = 41, 43, -5 with p = 0.012, 0.008, 0.82) are the exact values for 9 mice; the dandiset holds 9.
  • Data missingThree Vglut2 PPN mice (C3412, C3798, C4707) have no 5 Hz trains in their frequencies sessions, while the paper's Friedman statistic for PPN 1 s (24.8) needs at least 9 mice with all four frequencies.
  • Data missingSubject C4608 (SNr GABA, PPN) has no 4 s trains in its frequencies session; the conversion notes say they were recorded in a separate session, which is not in the dandiset.
  • Metadata errorThe dF/F series are stated in a.u. but hold percent (100 times (Gc - fit) / fit); a recomputation from the stored signals agrees with a median correlation of 0.9999 (durations) and 0.9988 (frequencies).
  • Metadata errorEvery session start time carries the offset -00:01, the local mean time of London that pytz gives when a time zone is attached with replace; the true offset is lost.
  • Metadata errorThe session description of the frequencies protocol gives an interval of 10 s between trains; the epochs and the Methods give 20 s.
  • OtherThirteen mice (SNr GABA and pan-DA, ids starting with B) have 10 trials per condition where the Methods state 5, and 30 mice have 16 s trains that the paper does not mention.
  • Published code disagreesThe conversion code names the 1 s block of the STN to SNr GABA frequencies sessions s1s10mW, suggesting 10 mW, while the epoch tables and the Methods give 5 mW.
  • Published code disagreesThe conversion repository's Python re-implementation of the dF/F forces the robust fit through the origin, saying the MATLAB version does so, while its own description of the MATLAB scripts includes an intercept.
  • Metadata errorThe files describe the modulation inconsistently. The excitation source descriptions give 465 nm modulated at 210 Hz and 405 nm at 330 Hz, as the Methods do, while the processed series descriptions give the calcium signal as demodulated at 330 Hz and the isosbestic signal at 210 Hz, as the conversion repository's description of the MATLAB scripts does. This attempt did not check which is right against the raw signal.
  • Description missingThe file names and session ids of nine Anxa1 mice carry no recording site, and every Anxa1 file lists both an SNc and a DLS fiber in its fiber photometry table, so the site rests on the name of the dF/F series alone.
  • OtherEight subject ids are written in lower case (c3015, c3016, c4379, c4708, c4709, c4977, c4978, c5113) while the others are upper case.
  • Paper inconsistentThe Results give F1,11 = 12.8 for the DLS frequency effect with 1 s trains for both STN (p = 0.0005) and PPN (p = 0.002); F(1, 11) = 12.8 gives p = 0.0043, and the data give F = 26.2 for STN. Two Friedman entries for Anxa1 terminals also do not fit their p-values (F = 11.5 with p = 0.0002, F = 15.5 with p = 0.015; with 3 df these give 0.0093 and 0.0014). F1,11 is also not possible for a one-way repeated-measures ANOVA in 7 or 9 mice. The Figure 5 legend says the Anxa1 STN frequency panels (N, O) show no significant effect of frequency, while the Results report significant effects for all three STN durations.
  • Methods not availableThe lab's MATLAB analysis scripts are not public; the preprint names custom MATLAB code and has no code availability statement. The conversion repository describes them.
  • OtherThe dandiset has no published version; this attempt used the draft as modified on 2026-09-01T15:27:47Z.

Notebooks

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

Reproduction Responses of SNr GABA and SNc dopamine neuron subtypes to STN and PPN input (Hadjas et al. 2025)

Tests the mouse fiber photometry findings of Hadjas et al. (2025) on dandiset 001528, which holds recordings from 120 mice during optogenetic stimulation of STN or PPN inputs to the substantia nigra. It compares responses of SNr GABA neurons, SNc pan-DA neurons, striatal dopamine release in TS and DLS, DA terminals, and Vglut2+ and Anxa1+ DA neurons across train durations and frequencies, using the lab's dF/F stored in the files. The human tissue counts of Figure 1 are not in the dandiset. All files

Verification

  • Round 1
    2026-10-18    Agreed with 24 of 25 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: Round 1. The first executed notebook with the conclusion cells and the summary removed, the helper module and the claims file, with the paper. The verifier queried the archive's asset list and metadata and tested the helper functions on synthetic inputs. It gave its own outcome for each claim; 24 of 25 agree with the record. It would give not_reproduced for fig5-anxa1-dls-inhibited, which the record has as blocked.
    • fig5-anxa1-dls-inhibited: the verifier’s outcome was “Not reproduced”. 2 of 6 significant with the DLS labels, n 5 and 4. Every mouse decreases except one in PPN 4 s, so the failure comes from sample size. With n = 5 the smallest two-sided Wilcoxon p is 0.0625 and with n = 4 it is 0.125, so three of the six tests cannot pass whatever the data show. The paper's W = -36 and -55 equal -n(n+1)/2 for n = 8 and 10, and t 6.4 with p 0.0004 needs df 7, so the paper analysed 8 and 10 DLS mice. The unsuffixed-recordings variant does not reproduce these statistics, so those recordings are not the paper's DLS data. The outcome reflects data missing from the archive, which the notebook never states as such.
  • Round 2
    2026-10-18    Agreed with 25 of 25 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: Round 2. The full executed notebook after the round-1 revision, the helper module, the claims file and the attempt record, with the paper. The verifier checked every conclusion, the Summary, the README and the record's notes and findings against the printed outputs, and gave its own outcome for each claim; it agrees with all 25. It found wording to correct in cell 70, cell 0, the README run time, and the word exactly for the cell-body match. In reply the README now gives about seven minutes (6.9 min in the round-2 run); the other changes are under the claims below.

Method differences

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

  • The rebound window (1 s after offset) and test are choices; the paper gives no statistic.fig4cf-dls-rebound fig5-anxa1-dls-rebound
  • Counted from the durations protocol; the frequencies protocol gives the same counts.cohort-sizes
  • The response window (mean during the train) and pre-stimulus window (same length, before onset) are choices; the paper does not state them.fig2-gaba-excited
  • All seven STN mice have 10 trials per condition, where the Methods state 5.fig2-gaba-excited
  • The conversion code names the STN 1 s block of these mice as 10 mW, while the files and the Methods give 5 mW; the analysis takes the files as they are.fig2-gaba-frequency
  • The paper does not give the window in which the peak is sought; the criterion fixed 0 to 2.25 s, and the variant 0 to 1.25 s matches the paper.fig3b-da-stn-250ms-peak
  • The paper's F and p fit four groups while three durations were tested; readings (a) and (b) match, and (b) gives the paper's value.fig3c-da-stn-duration
  • The paper does not say which train duration Figure 3D shows; the 1 s train was fixed in the criterion.fig3d-da-stn-frequency-ns
  • The paper's measure for this comparison is not stated; the mean during the train (and the area under the curve) were used, as for the STN comparison, which matches the paper there.fig3g-da-ppn-duration
  • The 1 s train was fixed in the criterion, as the paper does not name the duration.fig3h-da-ppn-frequency-ns
  • The paper does not state the window or test for this observation; the mean during 1 s trains (Figure 4E and 4H) against 0 was fixed in the criterion. The sentence cites both the 1 s panels and the 4 s panels (Figure S3F and S3L), and its account of summation over pulses fits longer trains; under the 4 s reading the effect holds for STN only.fig4eh-dls-5hz-increase
  • 8 DLS mice, where the paper has 9.figs3-terminals-opposite
  • 9 STN mice, where the legend gives 10; the paper's W and p values are the exact values for 9 mice.fig5-vglut2-excited
  • The PPN tests use the 7 of 10 mice that have all four frequencies; C3412, C3798 and C4707 have no 5 Hz trains in the dandiset. The paper's PPN 1 s Friedman statistic of 24.8 needs at least 9 mice (the maximum is 3n), so the paper had 5 Hz trains that are not deposited.fig5-vglut2-frequency
  • 5 and 4 mice, where the paper has 8 and 10 (see fig5-anxa1-dls-inhibited).fig5-anxa1-dls-frequency
  • 5 and 4 mice, where the paper has 8 and 10.fig5-anxa1-dls-rebound
  • The dandiset labels 8 and 10 mice as SNc where the paper analysed 5 and 4; the outcome uses the dandiset's labels as fixed in the criterion.figs4-anxa1-soma-inhibited
  • Anxa1 DLS recordings of 5 and 4 mice, where the paper has 8 and 10.fig5-opposite-subtypes

Provenance

Attempt record
001528-hadjas-2025-01
Paper
Parkinson’s Disease-vulnerable and -resilient dopamine neurons display opposite responses to excitatory input
Date
2026-10-18
Made by
An agent, run by CatalystNeuro
Dataset
DANDI:001528
Version
draft, modified 2026-09-01 15:27:47+00:00
Run on
GitHub Actions
Harness
Claude Code (GitHub Actions)
Model
claude-opus-5-5
Protocol
pilot-7

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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