Claims 43
From the paper Early dopamine disruption in the entorhinal cortex of a knock-in model of Alzheimer’s disease · claims file · checked 2026-10-21: ready
- units-recorded
In LEC layer 2/3 of young mice, 479 neurons were recorded from 5 WT mice and 846 from 5 APP-KI mice.
recorded 479 and 846 neurons from n = 5 young WT and n = 5 young APP-KI mice, respectively
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 1How it will be judged
Counts of sorted units from young WT and young APP-KI tetrode sessions. The putative principal cells (peak-trough width above 230 us and more than 100 spikes in the session, Methods) are counted as well and compared with 423 and 636 (Fig. 2d legend) and with the per mouse counts of Supplementary Fig. 2. Reproduced when both totals are within tolerance.
- ed4a-spike-type-distribution
The proportions of narrow, regular and wide spiking LEC L2/3 cells differ between young WT and young APP-KI mice.
Bottom, percentage of NS, RS, and WS cells in young WT and young APP-KI mice. ( p = 1.2e-23, Chi-squared test for comparing distributions
Extended Data Fig. 4a; Supplementary Table 1How it will be judged
All units classified by spike peak-trough width into NS (below 230 us), RS (230 to 390 us) and WS (above 390 us), the cut offs of Extended Data Fig. 4a; chi-squared test of the 3 by 2 table. The channel the width is read from is not given; readings (a) the channel with the largest mean amplitude, (b) the mean over the four channels. Reproduced when p < 0.05.
- ed4b-spike-width
Putative principal cells of LEC L2/3 have narrower spikes in young APP-KI mice than in young WT mice, while putative interneurons do not differ.
LEC L2/3 neurons in APP-KI mice showed decreasing spike widths compared to those of WT mice, suggesting alterations in spike generation mechanisms
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 1; Extended Data Fig. 4b; Supplementary Fig. 2bHow it will be judged
Peak-trough width as in ed4a-spike-type-distribution; principal cells are RS plus WS, interneurons NS (Supplementary Fig. 2b). Wilcoxon rank sum test on cells. Supplementary Table 1 gives p = 1.7e-30 for the principal cells where the legend gives 3.9e-15; either is significant. Reproduced when the principal cells are narrower in APP-KI at p < 0.05 and the interneurons do not differ at p < 0.05 (the paper's test, a claim of absence for that part). The per mouse t-test is shown as well.
- ed4c-higher-firing-rates
Mean firing rates of putative principal neurons and interneurons in LEC L2/3 are higher in young APP-KI mice than in young WT mice.
the mean firing rates of putative LEC L2/3 principal neurons and interneurons were both higher in APP-KI mice than those of WT mice
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 1; Extended Data Fig. 4c and 4dHow it will be judged
Mean firing rate of each cell over the associative learning session (Extended Data Fig. 4c), Wilcoxon rank sum test on cells, principal (RS and WS) and interneurons (NS) separately. The rate's definition is not given; readings (a) spike count over the whole recording of the session, (b) over the AB12 session's trial periods only. Reproduced when both cell classes have higher rates in APP-KI at p < 0.05; partially when one class does. The peak rate (not defined; read as the maximum of the 50 ms, sigma 100 ms smoothed rate) and the per mouse t-tests of Supplementary Fig. 2c, 2d are shown.
- fig2d-more-cue-responsive
At the end of the session (T5), 16% of LEC L2/3 principal neurons respond to at least one odor cue in young WT mice and 34% in young APP-KI mice; the distribution of response classes differs at T1, T3 and T5.
While 16% of LEC L2/3 neurons fired to at least one odor cue at T5 in WT mice, an excessive 34% of neurons exhibited cue responses in APP-KI mice
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 2; Fig. 2dHow it will be judged
Principal cells of all young sessions (correct and error). Each cell is classed at T1, T3 and T5 by the number of odor types (0 to 4) it responds to, as in Shared method, Spike response (odor period, p < 0.05), under readings D+ and D+-; T1, T3, T5 do not depend on the T-a, T-b readings. Chi-squared test of the class by strain table at each timepoint, Benjamini-Hochberg post hoc per class. Reproduced when, under one reading, both T5 percentages are within tolerance and the T5 chi-squared test has p < 0.05 with more responsive cells in APP-KI. The any-period variant of Shared method is shown. The printed chi2 of 2.29 cannot give p = 3.6e-9 on these counts and is not used as a target.
- ed5-more-odor-a-cells
Among LEC L2/3 cells, young APP-KI mice have a higher percentage of Odor-A responsive cells than young WT mice through T1 to T5.
Among these cue-responsive neurons in APP-KI mice, the percentage of Odor-A responsive cells was higher in APP-KI mice compared to those in WT mice
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 2; Extended Data Fig. 5; Supplementary Table 1How it will be judged
Response classes by odor combination (A, B, 1, 2, A-1, and so on, and none) from the responses of fig2d-more-cue-responsive, under the same readings, as a percentage of all principal cells. Chi-squared test of the class by strain table at T1, T3, T5, with Benjamini-Hochberg post hoc tests per class. Supplementary Table 1 gives the post hoc tests per combination class (A, 1, A-1, B-1, null), so the Odor-A class is the cells responding to A only; cells responding to A among others are shown as a variant. Reproduced when, under one of the D readings, the Odor-A class is larger in APP-KI at T1, T3 and T5 with a post hoc p < 0.05 at each; partially when that holds at one or two timepoints.
- fig2j-per-mouse-response-types
Analysed per mouse, the response type distribution of LEC L2/3 cells differs between young WT and young APP-KI mice at T5, with fewer non-responsive cells and more 1-odor cells in APP-KI mice.
Similar results were obtained when data were separated and analyzed per animal
Fig. 2j; Extended Data Fig. 3cHow it will be judged
Per mouse percentages of principal cells responding to 1, 2, 3 or 4 odors or none at T5, under the readings of fig2d-more-cue-responsive; two-way ANOVA type by strain on the 50 mouse-by-type values, Tukey post hoc. Reproduced when, under one reading, the interaction has p < 0.05 and the non-responsive percentage is lower in APP-KI with a Tukey p < 0.05.
- fig2g-wt-a1-generalized
In young WT mice, the PCA distance between Odor-A and Odor-1 population trajectories is slightly above the shuffle at T1 and below it from T2 to T5, so the two rewarded cues become similarly represented.
In WT mice, A-1 distance was slightly larger than the shuffle at T1, but became smaller than the shuffle through T2–T5, indicating generalized representations of rewarded cues during learning
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 3; Fig. 2e, 2g, 2h; Supplementary Fig. 4aHow it will be judged
PCA, shuffle and SI as in Shared method on the 423 young WT principal cells, correct and error sessions pooled, under the readings N1, N2, F1, F2, S1, S2, M1, M2 (method, all run) and T-a, T-b (alternatives). "Smaller than the shuffle" is a reading of the paper's words, with alternatives (a) below the mean shuffle distance (SI above 0), (b) below the 95th percentile threshold (the red line of Fig. 2g). Reproduced when, under the readings, the A-1 distance is above the shuffle at T1 and below it at each of T2 to T5; partially when below at three of the four. The shuffle thresholds (from Supplementary Table 1) are a check of the pipeline and are reported, not judged alone.
- fig2f-app-a1-separated
In young APP-KI mice, the Odor-A and Odor-1 trajectories stay far apart throughout the session, the A-1 distance remaining above the shuffle from T1 to T5.
However, A-1 distance in APP-KI mice remained above shuffle, indicating that Odors-A and -1 representations were not generalized together in APP-KI mice
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 3; Fig. 2f, 2g, 2h; Supplementary Fig. 4bHow it will be judged
As fig2g-wt-a1-generalized on the 636 young APP-KI principal cells. "Above shuffle" is read as (a) above the mean shuffle distance (SI below 0), (b) above the 95th percentile threshold. Reproduced when, under the readings, the A-1 distance is above the shuffle at each of T1 to T5; partially when at four of the five.
- fig2i-si-wt-above-app
Bootstrapped similarity between Odor-A and Odor-1 representations is higher in young WT than in young APP-KI mice across the session, significantly at T1a and T1c to T5.
A bootstrapping analysis confirmed the decreased A-1 similarity in APP-KI mice compared to WT mice throughout the session
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 3; Fig. 2i; Extended Data Fig. 8eHow it will be judged
Bootstrap as in Shared method (readings BS1 and BS2) on the SI of fig2g and fig2f, with the same PCA readings. Reproduced when, under the readings, WT minus APP-KI SI is positive with p < 0.05 at each of T1a, T1c, T2, T3, T4 and T5, the timepoints the paper reports as significant; partially when it is at three to five of them. Bootstrap p values below 0.001 cannot be matched exactly under BS2 and are compared as bounds.
- fig2k-per-mouse-distance
Analysed per mouse, the A-1 PCA distance at T5 is larger in young APP-KI mice than in young WT mice.
How it will be judged
PCA as in Shared method on each mouse's principal cells, per timepoint; A-1 mean distance per mouse; unpaired t-test WT against APP-KI at each timepoint, Benjamini-Hochberg FDR. Supplementary Table 1 (Extended Data Fig. 3d) lists the test at T1, T3 and T5 (NS, NS, p = 0.048). The family of the correction is a method detail left open, with readings (a) T1, T3 and T5, (b) the six odor pairs at each timepoint, (c) both together, all run under the rule for readings. Reproduced when, under the readings, the T5 A-1 distance is larger in APP-KI with corrected p < 0.05.
- fig2l-per-mouse-si
Analysed per mouse, the A-1 similarity index is lower in young APP-KI mice than in young WT mice across learning.
How it will be judged
Per mouse SI from fig2k-per-mouse-distance at T1a, T1b, T1c, T2, T3, T4, T5; two-way ANOVA strain by timepoint on the 70 values. Reproduced when the strain effect has p < 0.05 with WT higher.
- ed8-t1-a1-decrease
Within the first 10 trials, the A-1 distance of young WT mice decreases clearly from trials 1 to 3 (T1a) to trials 7 to 9 (T1c), while in young APP-KI mice the trajectories stay far apart.
We further subdivided T1 into trials 1–3 (T1a), 4–6 (T1b) and 7–9 (T1c) and observed clear decrease of A-1 distance from T1a to T1c
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 3; Extended Data Fig. 8How it will be judged
PCA as in fig2g-wt-a1-generalized on trials 1 to 3, 4 to 6 and 7 to 9 of each odor type. Reproduced when, under the readings, the WT A-1 distance at T1c is below that at T1a, the APP-KI A-1 distance stays above the shuffle at T1a, T1b and T1c (Extended Data Fig. 8b, "kept far apart through T1a to T1c"), and the WT minus APP-KI SI at T1c is positive in the bootstrap with p < 0.05; partially when the WT decrease holds and one other part fails.
- ed9-old-a1-separated
In old mice, Odor-A and Odor-1 representations generalize from T2 to T5 in WT mice but stay separated throughout the session in APP-KI mice.
In old age, generalization of Odors-A and -1 was observed through T2–T5 in WT mice, whereas representations for these two cues were again kept separated throughout the session in APP-KI mice
Results, Disrupted associative memory encoding in lateral entorhinal cortex layer 2/3 neurons, paragraph 3; Extended Data Fig. 9; Supplementary Fig. 5How it will be judged
As fig2g-wt-a1-generalized, fig2f-app-a1-separated and fig2i-si-wt-above-app on old principal cells. Supplementary Table 1 gives T3 p = 0.089 and T1a p = 0.17, so T3 is not required. Reproduced when, under the readings, the old WT A-1 distance is below the shuffle at each of T2 to T5, the old APP-KI distance is above it at each of T1 to T5, and the bootstrap difference is positive with p < 0.05 at T1b, T1c, T2, T4 and T5; partially when one or two of these timepoints fail.
- ed7-decoding-correct-error
In both young WT and young APP-KI mice, a decoder trained on Odor-A against Odor-B activity discriminates Odor-1 from Odor-2 in correct sessions but not in error sessions.
The decoding analysis showed that neural activity in correct sessions discriminated between Odor-1 vs. Odor-2, whereas activity in error session could not discriminate them in WT mice
Extended Data Fig. 7b and 7dHow it will be judged
Methods, Decoding analysis. Mean firing rates in 50 ms bins, 1 to 4 s after odor onset, normalized; binary support vector machine trained on Odor-A against Odor-B, tested on Odor-1 (as A) and Odor-2 (as B); 10 bootstraps of resampled data (Extended Data Fig. 7b); correct and error sessions apart (young WT 352 and 71 cells, APP-KI 411 and 225); timepoints T1a to T5 (Supplementary Table 1). The kernel is not given; the linear kernel, MATLAB's default for a binary SVM, is a standard choice and is recorded as a deviation. Method details left open, all run under the rule for readings. The test window, given as 2 to 5 s in the same paragraph, with readings (a) 1 to 4 s, (b) 2 to 5 s; what a sample is, with readings (c) each 50 ms bin's population vector, (d) each odor type's mean over the window; the normalization, with readings N1, N2 and a z-score per neuron. Reproduced when the session by time interaction has p < 0.05 in both strains and correct exceeds error sessions with Tukey p < 0.05 at each of T2 to T5 in both strains. The paper gives no test that error sessions are at chance; error-session performance is reported, not judged.
- fig3b-abeta-snc-above-vta
In young APP-KI mice, Abeta plaque density is higher in the SNc than in the VTA.
The density of Aβ plaques was higher in the SNc than that in the VTA
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 1; Fig. 3bHow it will be judged
Histology. Abeta-positive area above three standard deviations of background as a percentage of image area (Methods), per region and mouse. The test is named as rank sum in the text and signed-rank in Supplementary Table 1; both are run. Reproduced when SNc exceeds VTA with p < 0.05 under either.
- fig3d-th-fibers-spared
TH-positive axon density in the LEC does not differ significantly between APP-KI and WT mice, nor between ages.
Although there was a trend of decrease in the density of TH + axons of APP-KI mice, the effect was not significant across strain nor age
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 1; Fig. 3dHow it will be judged
A claim of absence, on the paper's test. TH-positive area in LEC images (3.4 to 3.8 mm AP) above three standard deviations of background, as a percentage of image area, per mouse; two-way ANOVA strain by age. Reproduced when neither the strain nor the age effect has p < 0.05; the effect sizes are reported.
- ed10-th-cells-spared
The density of TH-positive dopamine neurons in the VTA and SNc does not differ between APP-KI and WT mice.
We also measured the density of dopaminergic neurons in the VTA and SNc, finding no significant alteration between APP-KI and WT mice
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 1; Extended Data Fig. 10How it will be judged
A claim of absence, on the paper's test. TH-positive cell counts per image area in VTA and SNc (3.4 to 3.6 mm AP), per hemisphere or mouse; two-way ANOVA strain by age with Tukey post hoc. Reproduced when no strain effect, interaction or WT against APP-KI Tukey comparison at the same age has p < 0.05 (Supplementary Table 1 reports one significant pair, young WT against old APP-KI in SNc, which is across ages).
- ed1-abeta-onset
In APP-KI mice, Abeta accumulates with age, starting in the LEC at 2 months and in the VTA and SNc from 4 months.
age-dependent accumulation of amyloid-ß (Aβ) starts widely in cortical regions, including the LEC, at 2 months of age
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 1; Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 1; Extended Data Fig. 1How it will be judged
Abeta-positive area above three standard deviations of background as a percentage of image area (Methods), per region and age group (12 month WT, APP-KI at 1, 2, 3, 4, 6, 9 and 12 months, 4 mice each); one-way ANOVA with Tukey (Supplementary Table 1). The LEC F is 15.34 in Supplementary Table 1 and 3.72 in the Extended Data Fig. 1b legend; the SNc entry repeats the VTA numbers. Reproduced when the ANOVA has p < 0.05 in each region and 12 month APP-KI exceeds 12 month WT with Tukey p < 0.05 in each. The paper gives no test for the onset ages (2 months in the LEC, 4 months in the VTA and SNc); the group means are reported against them, not judged.
- fig4b-wt-dopamine-t1
In correct sessions of control mice, LEC dopamine fibers respond at T1 to prelearned Odor-A, to novel Odor-1 and to novel Odor-2; with learning the Odor-2 signal disappears while the Odor-A and Odor-1 signals remain to T5.
At T1, dopamine was released primarily during delay periods of prelearned rewarded Odor-A (mean z -scored GCaMP signal, 1.1 ± 0.24
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Fig. 4bHow it will be judged
Photometry as in Shared method, correct sessions of the 10 control hemispheres, mean over hemispheres (Supplementary Fig. 6a shows these data by timepoint). The window of the reported means is "delay periods", not given; alternatives G1, G2 and (G4) 2 to 3 s, the delay period of the spike analysis (Methods). The test against the precue period uses the 2 to 4 s window (G2, Supplementary Table 1); it is named rank sum in the text and Wilcoxon signed-rank in Supplementary Table 1, and both are run. Reproduced when all three T1 means are within tolerance under one window, all three are above precue at p < 0.05, and the Odor-2 signal at T5 is not significant while Odor-A and Odor-1 are.
- fig4c-app-dopamine-delayed
In APP-KI mice, Odor-1 dopamine signals emerge late, from T3, in correct sessions and are absent in error sessions (39% of sessions), while Odor-A signals stay intact.
In APP-KI mice, in contrast, signals for Odor-1 emerged in a delayed manner from T3 (Fig. 4c , top), while dopamine signals for Odor-A remained intact when mice learned the association
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Fig. 4c; Supplementary Fig. 6bHow it will be judged
Photometry as in Shared method, APP-KI hemispheres, correct and error sessions apart (correct when T5 performance exceeds 80%, at or above 80% as the alternative). Signal significance per timepoint against the 1 s precue by Wilcoxon signed-rank at p < 0.05 in the 2 to 4 s window (G2, Supplementary Table 1). The denominator of the 39% is not given, with alternatives (a) the sessions of the APP-KI photometry hemispheres, (b) the sessions of the APP-KI photometry mice, counted once per session. Reproduced when the error-session share is within tolerance under one alternative, Odor-1 is not significant at T1 and T2 and significant at T3 in correct sessions, not significant at any timepoint in error sessions, and Odor-A is significant at T1 and T5 in both.
- fig4d-app-odor1-dopamine-decreased
Across all sessions, LEC dopamine activity during Odor-1 trials is significantly lower in APP-KI mice than in WT mice at T1.
dopamine activity was significantly decreased in APP-KI mice during Odor-1 trials at T1
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Fig. 4dHow it will be judged
Per hemisphere mean z-scored GCaMP signal for Odor-1 at T1 to T5, correct and error sessions together, window G1 (1 to 4 s, Fig. 4d legend); two-way ANOVA strain by timepoint on the 90 values, Tukey post hoc. Reproduced when the interaction has p < 0.05 and WT exceeds APP-KI at T1 with Tukey p < 0.05; partially when only the T1 Tukey comparison holds. G2 and G3 are shown as variants.
- fig4e-correct-sessions-odor1-decreased
In correct sessions, Odor-1 dopamine activity at T1 is also lower in APP-KI mice than in WT mice, with no significant interaction for Odor-2.
Dopamine was also decreased in APP-KI mice during Odor-1 at T1 in correct sessions
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Fig. 4e; Supplementary Fig. 6cHow it will be judged
As fig4d-app-odor1-dopamine-decreased on correct sessions only. Reproduced when, under G1, the Odor-1 interaction and the T1 Tukey comparison have p < 0.05 with WT higher.
- fig4f-error-sessions-no-difference
In error sessions, dopamine activity does not differ between young WT and young APP-KI mice.
No difference was observed in error sessions
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Fig. 4fHow it will be judged
A claim of absence, on the paper's test. As fig4d-app-odor1-dopamine-decreased on error sessions, window G1, for each odor type. Supplementary Table 1 reports for these data strain main effects at p = 0.047 (Odor-1) and 0.0061 (Odor-2) together with no significant interaction and "NS for all pairs" in the Tukey tests, so the legend's "NS" is the interaction and the post hoc comparisons. Reproduced when, for each odor type, the strain by time interaction has p >= 0.05 and no Tukey comparison of WT against APP-KI at the same timepoint has p < 0.05; the strain main effects and effect sizes are reported.
- figs7-odor1-specific-decrease
The WT minus APP-KI dopamine difference at T1 is larger for Odor-1 than for Odor-A or Odor-B.
The difference for Odor-1 was significantly larger than that for Odor-A or Odor-B, suggesting specific decrease of dopamine for Odor-1
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Supplementary Fig. 7aHow it will be judged
How a WT minus APP-KI difference is formed per unit is not given; F(3,28) implies 8 values per odor and Supplementary Table 1 says 8 WT and 8 APP-KI units. The one construction the text and the degrees of freedom allow is the 8 APP-KI hemispheres each subtracted from the WT mean; it is used and recorded as a deviation. Window G1. One-way ANOVA over the four odors at T1, Tukey post hoc. Reproduced when Odor-1 exceeds Odor-A and Odor-B with Tukey p < 0.05.
- figs6d-dopamine-behavior-correlation
In APP-KI mice, the trial at which Odor-1 dopamine signals emerge correlates with the trial at which licking to Odor-1 is learned.
The delayed emergence of Odor-1 dopamine signals correlated well with slow learning of licking to Odor-1 in APP-KI mice
Results, Dysfunction of lateral entorhinal cortex dopamine activity, paragraph 2; Supplementary Fig. 6dHow it will be judged
Per session (Supplementary Fig. 6d), the trial after which five consecutive Odor-1 hits start, against the trial after which five consecutive Odor-1 trials have GCaMP signal above 3 SD; sessions without such a run are dropped. Method details left open, all run under the rule for readings. What the 3 SD is taken from, with readings (a) the SD of the precue baseline, (b) the SD of the session's signal; the window, with readings G1 and G2 (Shared method, Photometry). Reproduced when, under the readings, r is within tolerance and p < 0.05.
- fig1d-young-new-association-impaired
Young APP-KI mice perform worse than young WT mice on novel odor associations at T5 (78.6% against 90.6% correct).
Young WT mice performed at 90.6 ± 0.9% in T5, whereas young APP-KI performed at 78.6 ± 2.1%
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 2; Fig. 1c, 1dHow it will be judged
Behavioral performance as in Shared method (readings B1, B2), per mouse means over all sessions; two-way ANOVA odor pair (A/B, 1/2) by strain on the 54 values, Tukey post hoc. Reproduced when, under one reading, both means are within tolerance (the s.e.m.), the interaction has p < 0.05 and the 1/2 Tukey comparison has p < 0.05; partially when the tests hold and the means do not.
- fig1d-prelearned-retrieval-intact
Young and old APP-KI mice retrieve the prelearned Odor-A/B association as well as WT mice.
both young and old APP-KI mice showed intact performance for retrieving prelearned associative memories
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 2; Fig. 1d, 1gHow it will be judged
A claim of absence, on the paper's test. The Tukey comparison of A/B WT against A/B APP-KI in the ANOVAs of fig1d-young-new-association-impaired and fig1g-old-new-association-impaired. Reproduced when p >= 0.05 at both ages; the differences are reported.
- fig1e-young-correct-sessions
Young WT mice learn the new association in 77.5% of sessions, young APP-KI mice in 59.1%.
Young WT mice had correct sessions at 77.5 ± 6.1% among all tested sessions, whereas young APP-KI mice had correct sessions at 59.1 ± 5.5%
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 2; Fig. 1eHow it will be judged
Per mouse percentage of correct sessions (Odor-1/2 T5 performance above 80%, and at or above 80% as the variant, readings B1 and B2); unpaired t-test across mice. Reproduced when, under one reading, both means are within tolerance and p < 0.05.
- fig1g-old-new-association-impaired
Old APP-KI mice are further impaired on novel associations compared with old WT mice (67.9% against 84.9% correct at T5).
84.9 ± 1.8% correct trials for old WT mice versus 67.9 ± 2.0% for old APP-KI mice
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 3; Fig. 1f, 1gHow it will be judged
As fig1d-young-new-association-impaired, for old mice.
- fig1h-old-correct-sessions
Old WT mice learn the new association in 81.3% of sessions, old APP-KI mice in 47.3%.
Old WT mice correctly learned 81.3 ± 6.4% of all sessions, whereas APP-KI correctly learned 47.3 ± 6.5%
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 3; Fig. 1hHow it will be judged
As fig1e-young-correct-sessions, for old mice.
- figs1c-old-wt-decline
Old WT mice show a slight decline of novel association performance compared with young WT mice.
Notably, old WT mice showed a slight decline of associative memory compared to young WT mice
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 3; Supplementary Fig. 1cHow it will be judged
As fig1d-young-new-association-impaired with age in place of strain, WT mice only. Reproduced when the 1/2 performance is lower in old WT with Tukey p < 0.05.
- figs1f-prelearning-duration-similar
APP-KI and WT mice need comparable numbers of days to reach criterion in the prelearning (Odor-A/B) sessions.
APP-KI and WT mice showed comparable duration for the training with prelearning sessions using Odor-A and Odor-B
Results, Impaired associative memory formation in amyloid precursor protein knock-in mice, paragraph 3; Supplementary Fig. 1fHow it will be judged
A claim of absence, on the paper's test. Days of prelearning to reach 80% per mouse; two-way ANOVA strain by age, Tukey post hoc. Reproduced when neither Tukey comparison within age has p < 0.05 and the interaction has p >= 0.05.
- fig5c-optogenetic-rescue
Optogenetic stimulation of LEC dopamine fibers during Odor-1 trials improves young APP-KI mice's novel association performance at T5 (95.2% against 77.9% in control sessions).
stimulation: 95.2 ± 1.6% versus control: 77.9 ± 4.9% at T5
Results, Rescued memory by dopamine reactivation, paragraph 1; Fig. 5b, 5cHow it will be judged
As fig1d-young-new-association-impaired with session type (control, stimulation) in place of strain, per mouse means over sessions of each type. The interaction p is 0.045 in the text and 0.047 in the legend and Supplementary Table 1. Reproduced when, under one reading, both means are within tolerance and the 1/2 Tukey comparison has p < 0.05.
- fig5d-optogenetic-correct-sessions
The percentage of correct sessions rises with stimulation (86.9% against 50.1%).
The percentage of total correct sessions significantly increased with stimulation
Results, Rescued memory by dopamine reactivation, paragraph 1; Fig. 5dHow it will be judged
As fig1e-young-correct-sessions, stimulation against control sessions per mouse, with the paper's unpaired t-test (a paired test is shown as a variant).
- figs9a-all-odor-stimulation-no-rescue
Stimulating LEC dopamine fibers during all four odor types does not rescue associative learning in young APP-KI mice.
No rescuing effect was observed when dopamine axons were stimulated during all four odor types
Results, Rescued memory by dopamine reactivation, paragraph 1; Supplementary Fig. 9aHow it will be judged
A claim of absence, on the paper's test. As fig5c-optogenetic-rescue for the all-odor stimulation mice. Reproduced when the interaction has p >= 0.05.
- fig6b-ldopa-rescue
L-DOPA restores young APP-KI mice's novel association performance at T5 (82.6% against 67.1% with saline).
L- DOPA groups 82.6 ± 1.7% versus saline group 67.1 ± 4.2% at T5
Results, Rescued memory by dopamine reactivation, paragraph 2; Fig. 6a, 6bHow it will be judged
As fig1d-young-new-association-impaired with drug in place of strain, over the 5 injection days. Reproduced when, under one reading, both means are within tolerance and the 1/2 Tukey comparison has p < 0.05.
- fig6c-ldopa-correct-sessions
L-DOPA raises the percentage of correct sessions in young APP-KI mice (78.5% against 33.1%).
The percentage of total correct sessions significantly increased with L- DOPA treatment
Results, Rescued memory by dopamine reactivation, paragraph 2; Fig. 6cHow it will be judged
As fig1e-young-correct-sessions, L-DOPA against saline mice.
- fig6h-ldopa-restores-a1-similarity
In L-DOPA treated APP-KI mice, Odor-A and Odor-1 trajectories become close and the SI is above 0 from T1c to T5, while saline-treated APP-KI mice keep them separated with negative SI.
Saline-injected APP-KI mice showed separated trajectories for prelearned rewarded Odor-A and novel rewarded Odor-1 (Fig. 6e,g ), resulting in negative SI values ... As a result, SI values were above 0 from trials 7–9 (T1c) to T5
Results, Rescued memory by dopamine reactivation, paragraph 3; Fig. 6e to 6hHow it will be judged
PCA, shuffle and SI as in fig2g-wt-a1-generalized on the L-DOPA and saline principal cells. Reproduced when, under the readings, the L-DOPA A-1 SI is above 0 at each of T1c, T2, T3, T4 and T5 and the saline SI is below 0 at each of the same timepoints (the paper gives no timepoints for "negative SI values"; the L-DOPA range is used); partially when one or two timepoints fail.
- fig6i-ldopa-si-bootstrap
Bootstrapped A-1 similarity is higher with L-DOPA than with saline from T1c to T4.
The subtraction confirms higher similarity in the representations between Odor-A and Odor-1 in L -dopa treatment compared to that in saline control
Fig. 6i; Supplementary Table 1How it will be judged
As fig2i-si-wt-above-app, L-DOPA minus saline. Reproduced when, under the readings, the difference is positive with p < 0.05 at each of T1c, T2, T3 and T4; partially when at two or three of them. T5 (p = 0.12) is not required.
- fig6k-ps19-ldopa-rescue
L-DOPA also rescues novel association performance in young PS19 tau model mice (84.8% against 64.8% with saline).
L -DOPA groups 84.8 ± 3.8% versus saline group 64.8 ± 4.6% at T5
Results, Rescued memory by dopamine reactivation, paragraph 3; Fig. 6j to 6l; Supplementary Fig. 10How it will be judged
As fig6b-ldopa-rescue for PS19 mice.
- figs11-wt-ldopa-no-effect
L-DOPA has no effect on the associative learning of control WT mice.
No effect was observed in L -DOPA-treated control WT mice
Results, Rescued memory by dopamine reactivation, paragraph 3; Supplementary Fig. 11How it will be judged
A claim of absence, on the paper's test. As fig6b-ldopa-rescue for WT mice. Reproduced when the interaction has p >= 0.05.
- figs9b-odor2-stimulation-impairs-wt
Optogenetic stimulation of LEC dopamine fibers during Odor-2 trials impairs novel association learning in young WT mice.
The stimulation during Odor-2 impaired associative memory in WT mice
Supplementary Fig. 9b; Supplementary Table 1How it will be judged
As fig5c-optogenetic-rescue for the WT mice stimulated on Odor-2 trials, control against stimulation sessions in the same mice. Reproduced when the 1/2 performance at T5 is lower with stimulation with Tukey p < 0.05. The binomial test of correct sessions (p < 0.001) is shown. F(1,16) does not fit 4 mice in a 2 by 2 design (12 error degrees of freedom); the result is reported against the paper's numbers all the same.
Pipeline
- Paper
- done (1 of 1)
- Claims
- done
- Claims check
- done (ready)
- Attempt
- todo
- Questions
- none
- Verified
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