Dopamine signaling in the dorsomedial striatum promotes compulsive behavior (DANDI:000971)

Claims

From the paper Dopamine signaling in the dorsomedial striatum promotes compulsive behavior

Reproducing Seiler et al. (2022) from dandiset 000971 34

Notebook reproduce_seiler_2022.ipynb

Not reproducedResults, first section; Figure 1D
Mice trained on RI60 accept more shocks in the shock probes than mice trained on RR20 (main effect of schedule, F1,43 = 6.37, p < 0.05; schedule by time interaction, F1,43 = 4.54, p < 0.05), and RI60 mice accept more shocks on the late probe than on the early one (p < 0.01).
In the 32 RI60 and 5 RR20 mice with both probes, RI60 mice accept more shocks (early 11.38, late 16.31, against 4.80 and 6.60), but the schedule effect has p = 0.071 (F1,35 = 3.46) and the interaction p = 0.59. The RI60 rise has paired p = 0.032, 0.063 after Bonferroni correction, where the claim needs p < 0.01. Summing a probe day's files gives the same picture. The dandiset holds 6 RR20 mice (5 with both probes) against 9 in Figure 1D, so the test has little power on the RR20 side.
How the test differed from the paper’s method
- 5 RR20 mice with both probes where the paper has 9, and 32 RI60 mice where it has 36 (4 lack a probe in the dandiset).
- The test is a two-way mixed ANOVA on complete cases, in Python; the paper used Prism.
Not reproducedResults, third section; Figure 3F
The DMS rewarded-unrewarded peak score differs by phenotype (F2,33 = 8.16, p < 0.01) and changes across training (p < 0.001).
Mean DMS score PR 2.35, DPR 1.66, PS 1.05 z, the paper's order, but the phenotype effect has likelihood ratio p = 0.100 and neither stage alone is significant (p = 0.124 early, 0.270 late). The score rises from early to late (paired p = 0.046, 17 mice; model stage p = 0.088). Without the dropout step the phenotype p is 0.389. 51 scores from 34 mice. The mice with a score differ from Figure 3E (late PR 4, DPR 7, PS 10 against 5, 6, 13), so the comparison with F2,33 is not like for like.
How the test differed from the paper’s method
- Early and late RI60 only; the paper's test also includes RI30, which is not in the dandiset.
- Channel dropouts are left out (samples below half the channel median, with 1 s around them), a step the authors' code does not have; it was added after seeing that dropouts made some session z-scores near zero, and after the per-session scores had been seen. The authors' processing without it is shown and gives p = 0.389.
- One DLS recording with dropouts over 10% of samples is excluded, and one session without rewarded nosepokes (mixed clocks) has no score.
- A linear mixed model with a random intercept per mouse replaces Prism's mixed-effects analysis.
Not reproducedResults, fourth section; Figure 4G
The DLS rewarded-unrewarded peak score does not correlate with shocks received (r = -0.01, ns).
Pooled DLS score against shocks, r = 0.326, p = 0.024, n = 48, where the paper finds r = -0.01. Late pairs r = 0.374, p = 0.10; early pairs r = 0.103, p = 0.60. Without the dropout step r = 0.113, p = 0.45 (late 0.033, early 0.182), so the outcome depends on the artifact handling, a step chosen here and in neither the Methods nor the authors' code. The DLS labels are consistent with the data (the DLS response has the larger 2 to 10 s area, as the paper describes for DLS).
How the test differed from the paper’s method
- The pairing of scores and probes follows reading (a) of fig3g-dms-score-shock-correlation; the paper does not state it.
Not reproducedResults, fifth section; Figure 5F
Mice receiving DMS dopamine terminal stimulation on rewarded nosepokes (ChR2) escalate their nosepoking faster than EYFP and ChR2 Scrambled controls during FR1 and RI30.
In the pooled fit no ChR2 slope differs from a control (FR1 interaction p = 0.63 and 0.98, RI30 p = 0.82 and 0.49), and the pooled FR1 ChR2 slope (0.011) is not above the controls (0.051 and 0.005). Per-mouse slopes, a variant, put ChR2 above EYFP (p = 0.015) and Scrambled (p = 0.021) in FR1 but not in RI30. ChR2 mice nosepoke more in RI30 (7.75 against 4.01 and 4.21 per minute). The pooled fit mixes mice with 1 to 13 FR1 sessions, which the per-mouse slopes avoid. A mixed model with a random intercept and slope per mouse puts the FR1 ChR2 slope above ChR2 Scrambled (p = 0.034) and EYFP (p = 0.0075) but not in RI30 (p = 0.68 and 0.70); under that model the rule would give partially_reproduced. That FR1 fit converged only after a retry with lbfgs, warns that the MLE may be on the boundary and has a random intercept variance near zero, and a model with a random intercept only puts ChR2 above neither control (p = 0.46 and 0.33). The criterion fixed the pooled fit before the analysis, so the outcome stays.
How the test differed from the paper’s method
- The paper fits a segmental linear regression in Prism; the pooled least squares fit with a group by session interaction was chosen before the analysis.
- 33 DMS excitatory mice in the dandiset where the paper has 39.
Not reproducedResults, fifth section; Figure 5G
On the first shock probe ChR2 mice accept more shocks than EYFP mice (interaction of time and manipulation, F2,35 = 3.65, p < 0.05; Tukey p < 0.05); the difference fades by the second probe.
First probe ChR2 28.69, EYFP 21.86, Scrambled 20.67 shocks, the paper's order; Tukey ChR2 vs EYFP p = 0.51; group by probe interaction F2,29 = 1.95, p = 0.16 (paper F2,35 = 3.65).
How the test differed from the paper’s method
- 32 mice with both probes (13 ChR2, 12 Scrambled, 7 EYFP) where the paper's degrees of freedom imply 38.
Not reproducedResults, seventh section; Figure 7F
Mice receiving DLS dopamine terminal stimulation (ChR2, EYFP, ChR2 Scrambled) escalate their nosepoking at the same rates.
In FR1 the Scrambled slope (0.087) is below the EYFP slope (0.224), interaction p = 0.013 (F test of all group terms p = 0.034). ChR2 differs from neither control (p = 0.12 and 0.98); in RI30 no pair differs (p = 0.09 to 0.92). The difference is between the two control groups, not a ChR2 effect. A mixed model with a random intercept and slope per mouse finds no difference in slope (p = 0.43 to 0.96, FR1 EYFP vs Scrambled p = 0.76), but its FR1 fit has a singular random effects covariance, so those p values are weak evidence. A model with a random intercept only fits without warnings and finds no FR1 difference either (EYFP vs Scrambled p = 0.23). The FR1 difference rests on the pooled fit the criterion fixed.
How the test differed from the paper’s method
- The paper gives no test; the fit of fig5f-dms-chr2-escalation was used, judged on all three pairs.
Partially reproducedResults, first section; Figure 1E
RI60-trained mice take longer to complete the omission probe than RR20-trained mice (unpaired t-test, p < 0.05; n = 20 and 7).
RI60 mice take 33.97 min (n = 19) and RR20 mice 17.72 min (n = 4); unpaired t-test p = 0.070, Welch p = 0.0005. The direction holds without significance by the paper's test. The RR20 variance is 251 times smaller than the RI60 one, so the Student and Welch tests disagree.
How the test differed from the paper’s method
- 4 RR20 omission probes in the dandiset against 7 in the paper, and 19 RI60 against 20.
- Completion time is the time of the 50th reward, or 60 min when fewer were earned; the Methods give the 50 reward and 60 min limits but not how incomplete sessions were scored.
Partially reproducedFigure 2A; STAR Methods, Behavioral Analysis
RI60 mice are split by their shock probe counts into 9 punishment resistant (PR), 9 delayed punishment resistant (DPR) and 18 punishment sensitive (PS) mice, by the rule in the Methods (DPR when the count rises by more than 85%; otherwise PR when the early count exceeds 13).
The stored labels give 9 PR, 9 DPR and 18 PS, which match by construction; only the rule check is informative. The Methods rule agrees with the stored label for 31 of 32 mice with both probes; 048.392 (13 early, 18 late) is stored as PR but the rule's "more than 13" makes it PS. With 13 or more, 32 of 32 agree. The 85% cut is near the top quartile of change (87.7%), but the median early count is 9.0, so 13 is not the median of these mice. Summing a day's files gives 30 of 32.
How the test differed from the paper’s method
- Four RI60 mice have one probe in the dandiset and cannot be checked against the rule.
Partially reproducedResults, second section; Figure 2K
After a reward PS mice wait longer before nosepoking again (38 +- 15 s) than PR (21 +- 5 s) and DPR (22 +- 4 s) mice (one-way ANOVA p < 0.01; Tukey p < 0.01 for each).
PS mice wait longest (53.94 s, SD 44.67, maximum 171 s), PR 21.05 s, DPR 21.86 s. PR and DPR are within tolerance, the PS mean is above it (23 to 53 s); with each mouse's median session PS is 32.2 s. The two highest PS mice (139.298 at 171.0 s, 348.393 at 168.7 s) each have one session with a mean wait over 1000 s. ANOVA p = 0.017; Tukey PS > PR p = 0.045, PS > DPR p = 0.051.
How the test differed from the paper’s method
- The rewarded port entry (first port entry after a reward) and the wait (to the next active nosepoke) are defined here from the Results; the code for them is not published.
Partially reproducedResults, second section; Figure 2L
PS mice make fewer extra nosepokes between a rewarded nosepoke and the rewarded port entry than PR mice (PS 1.28 +- 0.85, PR 3.23 +- 1.65, DPR 2.1 +- 2.63; Tukey PS vs PR p < 0.05).
PS 1.61, PR 3.33, DPR 2.28 extra nosepokes per reward, all within the stated SDs; PS < PR but Tukey p = 0.117 (ANOVA p = 0.139).
How the test differed from the paper’s method
- Extra nosepokes are defined here from the Results (active nosepokes after a reward and before the rewarded port entry).
Partially reproducedResults, second section; Figure 2N
Averaged over RI60 training, PS mice earn fewer rewards per session (39.91 +- 7.39) than DPR mice (46.56 +- 4.49; PR 45.33 +- 4.33); one-way ANOVA p < 0.05, Tukey PS vs DPR p < 0.05.
Rewards per RI60 session, PS 39.12, DPR 44.98, PR 44.66, all within tolerance; ANOVA F = 4.02, p = 0.028; Tukey PS vs DPR p = 0.059, so the pairwise test fails. The result sits at the threshold. With the false start of 140.306 kept as a session of 0 rewards Tukey p is 0.048 (the first version of this attempt), and with one file per mouse-day (PS 39.98, DPR 46.16, PR 44.66) it is 0.044. The rule used (no active nosepoke and no reward) was set after round 1 and is the only one of the three that gives p above 0.05; other kept short files of 1 to 4 rewards fit the same false-start reason. The claim is borderline.
How the test differed from the paper’s method
- Training files with no active nosepoke and no reward are left out (one PS file of 170 s); other files count as sessions, also when a mouse has two or three on one day.
Partially reproducedResults, second section; Figure 2O
PR mice escalate their nosepoking as soon as they enter RI30, while DPR mice escalate later, during RI60.
RI30 rate PR 4.85 per minute, DPR 3.03 (Mann-Whitney p = 0.114), PS 2.22 (p = 0.0063), so part (i) fails on DPR. Median RI60 slope DPR 0.809, PR 0.494 nosepokes/min per day, so part (ii) holds (p = 0.289).
How the test differed from the paper’s method
- The paper shows this with a segmental linear regression in Prism; the measures here (RI30 rate and RI60 slope per mouse) were chosen before the analysis.
Partially reproducedResults, third section; Figure 3G
The DMS rewarded-unrewarded peak score correlates with the shocks a mouse receives in the shock probes (r = 0.53, p < 0.0001).
Reading (a), pooled early and late pairs, r = 0.170, p = 0.24, n = 49 (given as measured); (b) late pairs r = 0.014, p = 0.95; (c) early pairs r = 0.375, p = 0.045, n = 29. Only (c) is positive and significant, and it is below the tolerance around 0.53. The support is weak. Corrected for the three readings (c) has p = 0.13, and without the dropout step (c) gives r = 0.362, p = 0.053 and the pooled r is 0.100. The step leaves out more than 1% of samples in one DMS session of 51, but changes some scores a lot where it leaves out less (88.239 from 0.09 to 1.92, 048.392 from 0.02 to 1.81, 346.394 from 0.00 to 1.10).
How the test differed from the paper’s method
- The paper does not say which scores and probes form the pairs; three readings were listed before the analysis, none of which matches.
- RI30 scores, which may be among the paper's points, are not in the dandiset.
Partially reproducedResults, fifth section; Figure S5F (legend not available)
Under DMS ChR2 stimulation 100% of male mice and about 71% of female mice are PR.
7 of 7 male ChR2 mice are PR; 5 of 6 female ChR2 mice (83.3%), outside 71 +- 7.1%.
How the test differed from the paper’s method
- One female ChR2 mouse (126.286) has a single session in the dandiset and no probes.
Partially reproducedResults, sixth section; Figure 6G
DMS dopamine terminal inhibition on rewarded nosepokes delays punishment resistance; NpHR mice accept fewer shocks than EYFP mice on the second probe (Tukey p < 0.01).
Second probe NpHR 9.33 against EYFP 23.47 shocks (34 mice with both probes), Tukey p = 0.069. With all 35 mice that have a second probe p = 0.043. Mixed ANOVA group p = 0.056.
How the test differed from the paper’s method
- 34 DMS inhibitory mice with both probes; the paper's degrees of freedom (F2,36) imply 39.
ReproducedResults, first section; Figure 1F
Among RI60 mice, shocks received on the late probe and omission completion time are not significantly correlated (r = 0.42, ns).
Late probe shocks and omission time, r = 0.335, p = 0.175, n = 18 (paper r = 0.42, ns). With the early probe r = 0.592, p = 0.0076.
ReproducedResults, second section; Figure 2B
There is an interaction of phenotype and probe on shocks received (p < 0.0001), and only DPR mice receive significantly more shocks on the late probe than the early one.
Phenotype by probe interaction F2,29 = 26.37, p = 3e-07. DPR mice rise from 11.56 to 32.11 shocks (Bonferroni p = 0.00041); PR (23.50 to 20.50) and PS (7.00 to 6.47) do not change.
How the test differed from the paper’s method
- 32 mice with both probes against 36; F2,29 where the paper gives F3,40.
ReproducedResults, second section; Figure 2C
During RI60 training PR and DPR mice nosepoke at higher rates than PS mice (main effect of phenotype, p < 0.0001).
Active nosepokes per minute over RI60 training, PR 14.20, DPR 12.79, PS 5.27; ANOVA p = 4.9e-06; Tukey PR > PS p below 0.0001, DPR > PS p = 0.0003; mixed model over 492 sessions p = 2.3e-06. With the empty files kept p = 4.3e-06, with one file per mouse-day p = 7.3e-06. Sex and phenotype are confounded (17 of 18 PS mice female, 8 of 9 PR male).
How the test differed from the paper’s method
- The main test is a one-way ANOVA on per-mouse means; the paper used a mixed-effects analysis over days, shown as a variant.
- Training files with no active nosepoke and no reward are left out (one PS file of 170 s here, which holds inactive nosepokes and port entries).
ReproducedResults, second section; Figure 2D
PR mice take longer than PS mice to complete the omission probe (PR 51.50 +- 17, PS 27.92 +- 13.65; one-way ANOVA F2,18 = 4.36, p < 0.05; Tukey PR vs PS p < 0.05).
PR 51.65 min (n = 4), PS 28.06 min (n = 10), DPR 31.67 (n = 5); ANOVA F2,16 = 3.85, p = 0.043; Tukey PR vs PS p = 0.037. Three of four PR mice reach 60 min.
How the test differed from the paper’s method
- The Results print the values in seconds; they are read as minutes (the Methods' median split is at 29 minutes).
- 10 PS mice where the paper has 11.
ReproducedResults, second section; Figure 2M
PS mice have longer inter-reward intervals (79.77 +- 26.54 s) than PR (71.2 +- 32.3 s) and DPR (69.58 +- 35.18 s) mice (Kolmogorov-Smirnov, p < 0.0001 for each).
Pooled RI60 intervals average PS 81.75 s, PR 71.96 s, DPR 69.57 s; KS PS vs PR p = 5e-30, PS vs DPR p = 3.3e-33. Per-mouse means give ANOVA p = 0.033.
How the test differed from the paper’s method
- The Methods define the interval from rewarded nosepoke to rewarded nosepoke and cite Figure 2L for it; reward times are used, which coincide with rewarded nosepokes in these files.
ReproducedResults, first section; Figure S1I (legend not available)
RI60-trained mice earn more rewards per training session than RR20-trained mice (unpaired t-test, p < 0.0001).
RI60 41.97 against RR20 22.63 rewards per session, t-test p = 5.4e-07, not below the 0.0001 stated. With the 21 empty files kept as sessions of 0 rewards (the 20 RR20 files that hold port entries only and the RI60 false start), RR20 15.38, RI60 41.89 and p = 1.4e-11.
How the test differed from the paper’s method
- 6 RR20 mice where the paper has 9 (or 7 in the Methods).
- 20 RR20 files of four mice hold port entries only and are left out, with one RI60 false start.
ReproducedResults, second section; Figure S2B (legend not available)
Male mice accept more shocks than female mice in the shock probes (main effect of sex, F1,35 = 26.19, p < 0.0001).
Males early 16.58 and late 23.25, females 8.25 and 12.15; sex effect F1,30 = 9.81, p = 0.0039. The paper's p < 0.0001 does not hold. Sex is confounded with phenotype (PR 8 males of 9, PS 17 females of 18).
How the test differed from the paper’s method
- The supplementary legend was not available; the test is a two-way mixed ANOVA of sex and probe.
ReproducedResults, third section; Figure 3H
The DMS rewarded-unrewarded peak score does not correlate with omission completion time (r = 0.1, ns).
Late DMS score against omission time, r = 0.014, p = 0.96, n = 12 (95% interval -0.56 to 0.58); pooled r = -0.050, p = 0.80. With 12 mice the test has little power.
How the test differed from the paper’s method
- 12 mice with a late score and an omission probe.
ReproducedResults, fourth section; Figure 4F
The DLS rewarded-unrewarded peak score has no significant effect of phenotype.
Phenotype likelihood ratio p = 0.48 (per stage p = 0.61 and 0.47); stage p = 0.034, as the paper also finds a training effect in DLS.
How the test differed from the paper’s method
- No RI30 stage; dropout step as for fig3f-dms-score-phenotype (without it p = 0.68).
ReproducedResults, fourth section; Figure 4H
The DLS rewarded-unrewarded peak score does not correlate with omission completion time (r = -0.21, ns).
Late DLS score against omission time, r = 0.311, p = 0.32, n = 12 (paper r = -0.21, ns); 95% interval -0.32 to 0.75, so the test has little power.
ReproducedResults, fifth section; Figure 5H
ChR2 mice are very likely to be classified PR, while EYFP and ChR2 Scrambled mice are distributed across phenotypes as expected.
PR in 12 of 13 ChR2 (92%), 5 of 7 EYFP (71%), 6 of 12 Scrambled (50%); Fisher ChR2 against both controls p = 0.0497. The control PR fractions are higher than in the fiber photometry cohort (19%).
How the test differed from the paper’s method
- Phenotypes are computed with the Methods rule, as the dandiset stores none for optogenetic mice.
ReproducedResults, fifth section; Figure 5I
DMS dopamine terminal stimulation does not change omission probe performance.
ChR2 25.79, Scrambled 35.53, EYFP 37.29 min; ANOVA p = 0.17, Kruskal-Wallis p = 0.14.
ReproducedResults, sixth section; Figure 6H
The NpHR group has more PS mice, and the NpHR Scrambled group more PR mice, than the EYFP group.
PS in 8 of 9 NpHR (89%) against 5 of 15 EYFP (33%), Fisher p = 0.013; PR in 6 of 10 NpHR Scrambled (60%) against 6 of 15 EYFP (40%), p = 0.43. The NpHR effect is in both sexes here (3 of 4 females and 5 of 5 males PS).
How the test differed from the paper’s method
- Phenotypes computed with the Methods rule.
ReproducedResults, sixth section; Figure 6I
DMS dopamine terminal inhibition does not change omission completion time.
EYFP 28.74, NpHR 21.47, NpHR Scrambled 27.82 min; ANOVA p = 0.21.
ReproducedResults, seventh section; Figure 7G
DLS dopamine terminal stimulation does not change the number of shocks received.
Group p = 0.055, group by probe p = 0.068, 31 mice with both probes. EYFP mice rise most (19.11 to 32.89).
How the test differed from the paper’s method
- 4 DLS mice lack a late probe in the dandiset.
ReproducedResults, seventh section; Figure 7H
DLS ChR2, EYFP and ChR2 Scrambled mice have similar distributions of PR, DPR and PS.
Chi-square p = 0.12 on a 3 x 3 table with smallest expected count 1.5; ChR2 mice include no DPR.
How the test differed from the paper’s method
- The paper gives no test; a chi-square test was chosen before the analysis.
ReproducedResults, seventh section; Figure 7I
DLS dopamine terminal stimulation does not change omission completion time.
ChR2 28.44, Scrambled 33.51, EYFP 36.08 min; ANOVA p = 0.53.
ReproducedResults, third section; Figure S3A-B (legend not available)data in Zenodo doi:10.5281/zenodo.11266654 (Densitometry.xlsx)
Heterozygous DAT-IRES-cre mice do not have reduced DAT protein in DMS or DLS compared with wild-type mice.
DAT/actin of het samples is 131.3% of the WT mean in DMS (t-test p = 0.41) and 74.7% in DLS (p = 0.20). The table holds females only, 3 WT and 4 het samples per region, named as lanes of one WT mouse (410) and one het mouse (484); the male samples of Figure S3A are not in it.
How the test differed from the paper’s method
- Females only; the paper's test is in a legend that was not available, so an unpaired t-test was used.
BlockedResults, sixth section; Figure 6F· Data missing from the dandisetverifier disagreed at first
DMS dopamine terminal inhibition impairs initial learning; 25% of NpHR and 22% of NpHR Scrambled mice in group 1 failed FR1, and 29% of NpHR mice in group 2 failed RI30, and were dropped.
The dandiset holds 13 NpHR, 13 NpHR Scrambled and 16 EYFP mice, where Figure 6F counts 16, 15 and 16. The shortfall (3, 2, 0) equals the mice the paper drops (about 4 NpHR, 2 NpHR Scrambled) less the one NpHR mouse deposited and flagged as not learning (270.476, no RI60). So the dropped mice are, but for that one, not in the dandiset. The 'Did Not Learn' flag also marks an EYFP mouse that reached RI60 (244.465), so it is not the paper's dropout criterion, and no file says which group (1 or 2) a mouse is in. Blocked under the criterion, as the dandiset does not say which mice were dropped.

Not tested in a notebook 4

4 data missing from the dandiset

BlockedResults, third section; Figure 3E· Data missing from the dandiset
Peaks in DMS dopamine axon activity at rewarded nosepokes emerge during RI30 in PR mice, and more slowly across RI60 in DPR mice.
The dandiset holds photometry for 53 RI60 sessions, 9 RR20 sessions and one session described as a probe test, and none for RI30, so the emergence of peaks during RI30 cannot be tested.
BlockedResults, first section; Figure S1A· Data missing from the dandiset
The 0.2 mA shock is aversive in a fear conditioning test, in males and females.
No fear conditioning session or freezing score is in the dandiset; every subject belongs to the photometry cohort, an optogenetic cohort or the western blot. The paper says data are available on request and names no archive.
BlockedResults, third section; Figure S3C-D· Data missing from the dandiset
Heterozygous DAT-IRES-cre mice are not hyperactive in a novel open field.
No open field tracking is in the dandiset or in another public archive the paper or the dandiset names.
BlockedFigures 3C and 4C· Data missing from the dandiset
GCaMP7b is expressed in TH-positive dopamine neurons of medial SNc (n = 572 cells) and of medial and lateral SNc (89.56% of GCaMP neurons TH-positive).
No histology images or cell counts are in the dandiset or in another public archive the paper or the dandiset names.

Findings about the data

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

Data missingThe Methods say photometry was recorded during RI30 and on both shock probes, but the dandiset holds photometry only for RI60 and RR20 training (62 sessions) and one session described as a probe test. The RI30 stage of Figures 3E-F and 4E-F cannot be tested.
Data missingMice are missing against the paper. 6 RR20 mice against 9 in Figure 1D (7 in the Methods), 33 DMS excitatory mice against 39, 42 DMS inhibitory mice against 47 in Figure 6F, and 35 DLS excitatory mice against 36. Of the photometry RI60 mice, 028.392 and 62.207 have no late probe and 89.247 and 78.214 no early one; several optogenetic mice lack a late probe.
Data missingThe fear conditioning (Figure S1A), open field (Figure S3C-D) and histology (Figures 3C, 4C and the probe placements) are not in the dandiset, and the paper says data are available on request.
Description missingOptogenetic mice have no stored phenotype (the notes read 'Punishment Group nan'), and the DMS inhibitory files do not say whether a mouse belongs to group 1 (light from FR1) or group 2 (light from RI30). Only two mice carry a 'Did Not Learn' flag, one of them an EYFP control, while the paper drops NpHR and NpHR Scrambled mice.
OtherThe 137 files of the group 'Opto-DLS-Excitatory-Unknown' repeat sessions of mice that are also deposited under a named arm; 135 share subject and start time with a named file, and those loaded here have identical events. They count the same sessions twice if taken at face value.
Metadata errorMouse 290.407 is filed under two experiments, 24 files as DMS excitatory ChR2 Scrambled and 2 (plus 2 'Unknown') as DLS excitatory ChR2.
File format errorIn shock probes on the left nosepoke, the reward series is named right_reward_times while its times are left nosepokes (151 files).
File format errorIn the stitched photometry session of 332.393 on 2020-07-28, the reward times are MedPC times that coincide with no nosepoke time, while the nosepokes and port entries are TDT times, so rewarded nosepokes cannot be identified.
OtherSeveral photometry recordings hold dropouts where a raw channel falls near zero (6 sessions reach |z| above 50 after the authors' processing, up to 1758), and in one (141.308, 2019-08-09) the DLS channels drop out through most of the recording. The dandiset does not mark these or say which recordings the paper excluded for artifacts.
Metadata errorThe fiber photometry table stores the fiber coordinates without the signs the Methods give (DV 2.8 for -2.8 and DLS AP 0.1 for -0.1).
Published code disagreesThe authors' MATLAB code comments call Dv1A the control and Dv2A the GCaMP signal, while the conversion and the files take Dv1A as the DMS 465 nm signal. The data side with the files (a larger rewarded response as labelled than swapped in 46 of 61 DMS sessions).
Selection not documentedMouse 048.392 is stored as PR with 13 shocks on its early probe, where the Methods classify as PR mice with more than 13, and the Methods call 13 a median split while the median early count of the RI60 mice is 9. How the stored labels were assigned is not documented.
Paper inconsistentThe Results give omission completion times in seconds (PR 51.50, PS 27.92), but sessions last at most 60 minutes and the Methods split omission times at 29 minutes; the data fit minutes. The Methods give 26 DMS inhibitory mice and 7 RR20 mice, Figure 6F counts 47 and Figure 1D 9.
OtherThe Zenodo densitometry table the dandiset names holds female samples only, labelled as three lanes of one wild-type mouse and four of one heterozygous mouse, while the dandiset's blot images include males.
Data missing20 RR20 training files (mice 96.259, 97.257, 99.257 and 100.258, 2019-04-29 to 2019-05-03) hold port entries only, with no nosepoke or reward series, so those sessions' nosepokes and rewards are not in the dandiset.
OtherSeveral fiber photometry mice have two or three RI60 files on one day (11 mouse-days), most a short file of 0 to 7 rewards beside a full session, some not (81.236 on 2019-02-06 has 6, 28 and 42 rewards). The dandiset does not say which file is the day's training session.
Data missingFigure 6F counts 16 NpHR, 15 NpHR Scrambled and 16 EYFP mice; the dandiset holds 13, 13 and 16. The mice missing are about the number the paper dropped for not learning, so the dropped mice are mostly not deposited, and the 'Did Not Learn' flag marks one NpHR mouse and one EYFP mouse that reached RI60.
OtherIn 45 of 64 RR20 training files with rewards, the reward times coincide with no nosepoke time, unlike RI60 and FR1 files; the relation of RR20 rewards to nosepokes is not described.

Notebooks

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

Reproduction Dorsomedial striatal dopamine and compulsive reward seeking (Seiler et al. 2022)

Tests the findings of Seiler, Cosme, Sherathiya, Schaid, Bianco, Bridgemohan and Lerner (2022) on dandiset 000971, which holds the operant behavior of a fiber photometry cohort and three optogenetic cohorts, dual-site photometry from DMS and DLS dopamine axons during RI60 and RR20 training, and western blot images. It tests the shock probe phenotypes and their behavior, the DMS and DLS rewarded-unrewarded peak scores, and the effects of DMS and DLS terminal manipulations. RI30 and shock probe photometry, fear conditioning, open field and histology are not in the dandiset. All files

Reproducing Seiler et al. (2022) from dandiset 000971
reproduce_seiler_2022.ipynbExecuted, with outputs · Source

Verification

Round 1
2026-10-18
Agreed with 37 of 38 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 checked the archive's asset list and metadata for the blocked claims and tested helper functions on synthetic inputs. It agreed with 37 of the 38 outcomes and would make fig6-nphr-learning-dropout blocked. Its other points and the responses not tied to one claim are as follows. B10 (events outside a recording dropped silently) - the notebook now prints the events kept, 2336 of 2337 rewarded and 10892 of 10916 unrewarded. C (Figure S1 to S7 legends not in the PMC text) - not resolved; the supplementary legends could not be obtained here either.
- fig6-nphr-learning-dropout: the verifier’s outcome was “Blocked”. Per arm the dandiset has NpHR 13, Scrambled 13 and EYFP 16 mice against 16, 15 and 16 in Figure 6F. The shortfall equals the paper's dropouts minus one deposited and flagged NpHR mouse, so most dropped mice were never deposited. The 'Did Not Learn' flag also marks an EYFP mouse that reached RI60, so it is not the paper's dropout criterion, and no file says which mouse is in group 1 or 2. This makes the claim blocked, not testable (B4).
Round 2
2026-10-18Agreed with 38 of 38 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, with its conclusions and summary, the helper module, the claims file and the attempt record. The verifier did not re-download the paper. It agreed with all 38 outcomes, and found that all round-1 points but the supplementary legends are resolved or disclosed. Its general point that the runtime of about 25 minutes matches the output needs no reply; the last runs took 883 and 892 s, and the README now says 15 to 25 minutes.

Method differences

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

5 RR20 mice with both probes where the paper has 9, and 32 RI60 mice where it has 36 (4 lack a probe in the dandiset).fig1d-ri60-vs-rr20-shocks
The test is a two-way mixed ANOVA on complete cases, in Python; the paper used Prism.fig1d-ri60-vs-rr20-shocks
4 RR20 omission probes in the dandiset against 7 in the paper, and 19 RI60 against 20.fig1e-omission-ri60-longer
Completion time is the time of the 50th reward, or 60 min when fewer were earned; the Methods give the 50 reward and 60 min limits but not how incomplete sessions were scored.fig1e-omission-ri60-longer
Four RI60 mice have one probe in the dandiset and cannot be checked against the rule.fig2a-phenotype-rule
32 mice with both probes against 36; F2,29 where the paper gives F3,40.fig2b-only-dpr-increase
The main test is a one-way ANOVA on per-mouse means; the paper used a mixed-effects analysis over days, shown as a variant.fig2c-nosepoke-rate
Training files with no active nosepoke and no reward are left out (one PS file of 170 s here, which holds inactive nosepokes and port entries).fig2c-nosepoke-rate
The Results print the values in seconds; they are read as minutes (the Methods' median split is at 29 minutes).fig2d-omission-pr-vs-ps
10 PS mice where the paper has 11.fig2d-omission-pr-vs-ps
The rewarded port entry (first port entry after a reward) and the wait (to the next active nosepoke) are defined here from the Results; the code for them is not published.fig2k-ps-wait-longer
Extra nosepokes are defined here from the Results (active nosepokes after a reward and before the rewarded port entry).fig2l-extra-nosepokes
The Methods define the interval from rewarded nosepoke to rewarded nosepoke and cite Figure 2L for it; reward times are used, which coincide with rewarded nosepokes in these files.fig2m-inter-reward-interval
Training files with no active nosepoke and no reward are left out (one PS file of 170 s); other files count as sessions, also when a mouse has two or three on one day.fig2n-rewards-per-session
The paper shows this with a segmental linear regression in Prism; the measures here (RI30 rate and RI60 slope per mouse) were chosen before the analysis.fig2o-escalation-timing
6 RR20 mice where the paper has 9 (or 7 in the Methods).figs1i-ri60-more-rewards
20 RR20 files of four mice hold port entries only and are left out, with one RI60 false start.figs1i-ri60-more-rewards
The supplementary legend was not available; the test is a two-way mixed ANOVA of sex and probe.figs2b-males-more-shocks
Early and late RI60 only; the paper's test also includes RI30, which is not in the dandiset.fig3f-dms-score-phenotype
Channel dropouts are left out (samples below half the channel median, with 1 s around them), a step the authors' code does not have; it was added after seeing that dropouts made some session z-scores near zero, and after the per-session scores had been seen. The authors' processing without it is shown and gives p = 0.389.fig3f-dms-score-phenotype
One DLS recording with dropouts over 10% of samples is excluded, and one session without rewarded nosepokes (mixed clocks) has no score.fig3f-dms-score-phenotype
A linear mixed model with a random intercept per mouse replaces Prism's mixed-effects analysis.fig3f-dms-score-phenotype
The paper does not say which scores and probes form the pairs; three readings were listed before the analysis, none of which matches.fig3g-dms-score-shock-correlation
RI30 scores, which may be among the paper's points, are not in the dandiset.fig3g-dms-score-shock-correlation
12 mice with a late score and an omission probe.fig3h-dms-score-omission-no-correlation
No RI30 stage; dropout step as for fig3f-dms-score-phenotype (without it p = 0.68).fig4f-dls-score-no-phenotype
The pairing of scores and probes follows reading (a) of fig3g-dms-score-shock-correlation; the paper does not state it.fig4g-dls-score-shock-no-correlation
The paper fits a segmental linear regression in Prism; the pooled least squares fit with a group by session interaction was chosen before the analysis.fig5f-dms-chr2-escalation
33 DMS excitatory mice in the dandiset where the paper has 39.fig5f-dms-chr2-escalation
32 mice with both probes (13 ChR2, 12 Scrambled, 7 EYFP) where the paper's degrees of freedom imply 38.fig5g-dms-chr2-more-shocks-early
Phenotypes are computed with the Methods rule, as the dandiset stores none for optogenetic mice.fig5h-dms-chr2-mostly-pr
One female ChR2 mouse (126.286) has a single session in the dandiset and no probes.figs5f-chr2-pr-by-sex
34 DMS inhibitory mice with both probes; the paper's degrees of freedom (F2,36) imply 39.fig6g-nphr-fewer-shocks-late
Phenotypes computed with the Methods rule.fig6h-nphr-more-ps
The paper gives no test; the fit of fig5f-dms-chr2-escalation was used, judged on all three pairs.fig7f-dls-escalation-similar
4 DLS mice lack a late probe in the dandiset.fig7g-dls-stim-no-shock-effect
The paper gives no test; a chi-square test was chosen before the analysis.fig7h-dls-similar-phenotypes
Females only; the paper's test is in a legend that was not available, so an unpaired t-test was used.figs3ab-dat-protein-not-reduced

Provenance

Attempt record: 000971-seiler-2022-01
Paper: Dopamine signaling in the dorsomedial striatum promotes compulsive behavior
Date: 2026-10-18
Made by: An agent, run by CatalystNeuro
Dandiset version: 0.261013.1707
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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