Correction to “Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression-like behaviour in C57BL/6J mice”

Mineur, Y.S., Mose, T.N., Blakeman, S., & Picciotto, M.R. (2018). Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression-like behaviour in C57BL/6J mice. British Journal of Pharmacology, 175(11): 1903–14. PMC5979617

Following an initial corrigendum, we realized that parts of the manuscript text and conclusions had not been updated accordingly, which could cause confusion for the reader. Changes to the text are underlined:

- The Results should read: MLA has an antidepressant-like effect in the forced swim test, but does not affect response to tail suspension and social defeat stress.

In the tail suspension test, an ANOVA showed that there was an overall effect of treatment in female (F2, 27 = 15.8) and male mice (F2, 27 = 4.8). In female mice, post hoc analyses revealed that GTS-21 had no effect compared with saline, but that MLA significantly decreased the time spent immobile, despite significant variability due to several animals moving continuously (Table 2). In male mice, there was no significant effect on immobility following GTS-21 treatment, whereas MLA treatment resulted in a non-significant (p = .06) decrease in time spent immobile (Figure 1A).

- In the Discussion, the text should read: Systemic administration of the α7 nAChR antagonist MLA resulted in anxiolytic- and limited antidepressant-like effects, as has been observed previously in male mice (Andreasen et al., 2009). MLA administration decreased immobility in the tail suspension test only in female mice, but high variability was observed in the behavioural outcomes in both sexes, making the results difficult to interpret.

We apologize if the previous version of the Corrigendum was confusing to the readers.

Furthermore, while updating the text and in partnership with Wiley, an independent statistical expert, and the BJP editors, we thoroughly reviewed all experimental data, including raw data files, values, group labels, and statistical analyses, comparing them with the information presented in the published article. During this process, we identified a few issues that were missed/introduced during the review corrections. These do not affect the conclusions of the study, but nonetheless warrant clarification:

- During the revision process a scatterplot of all datapoints was added to Figure 2, but the datapoints were somewhat shifted compared to the bar graph values. The statistics and conclusions are unaffected, and the realigned version is included below.

- In the Methods section (Statistics) and Legend 4 we used a (Fischer's) Protected Least Square Differences, not a “Partial” Least Square Differences, an incorrect description of “PLSD”. Note that a Fischer's PLSD was used in the knockdown studies, but the behavioural pharmacological studies used a t-test with Bonferroni corrections. This is described in the figure legends but was not specified in the Methods section where only the PLSD was mentioned.

- In the Results section (c-fos analysis): “There was an overall pretreatment (physostigmine) by treatment (MLA) interaction (F(1, 16) = 9.9), in male mice,(…)”, should read “There was an overall pretreatment (physostigmine) by treatment (MLA) interaction in female (F(1, 16) = 9.9), and male mice (F(1, 16) = 24.1) (…)”.

- In the Results section (α7 knockdown experiments, FST): “In male mice, there was an overall increase in time spent immobile induced by physostigmine, which was blunted by α 7 knockdown in hippocampus, although the interaction between treatment and knockdown did not reach significance (F(1, 36) = 3.9; Figure 4B). The effect of physostigmine at 5 min was still significantly greater than that of saline, in control mice or with α7 knockdown overall, as revealed by post hoc further analyses (F(1, 36) = 23.4).”

Indeed, the p value for this two-way ANOVA (knockdown by treatment) is p = .056, but it is BJP policy to remove all p values and to only disclose significance under a set threshold (p = .05 in our case).

- In the Results section (α7 knockdown experiments, FST), the text should read: “At 10 min, further analyses showed that there was complete reversal of the physostigmine effect (F(1, 36) = 17.1 4.7).

- In the Results section (α7 knockdown experiments), the text should read: “Physostigmine significantly reduced ambulatory activity (…) in male mice (F(1, 41) = 200.1) F(1, 34) = 178.9).” The p values are still strongly significant.

- In the Discussion, we state that “MLA significantly decreased DG c-fos expression in male (…)”, but it should have been specified, as in the Results, that “MLA significantly decreased DG c-fos expression induced by physostigmine in male (…)”.

We apologize to the readers for these oversights during the final review process.