Sex and estrous cycle affect experience-dependent plasticity in mouse primary visual cortex

Rachel W. Schecter; Cambria M. Jensen; Jeffrey P. Gavornik

doi:10.1371/journal.pone.0282349

Peer Review History

Original SubmissionOctober 3, 2022
12 Dec 2022 Decision Letter - Dragan Hrncic, Editor PONE-D-22-27303Sex and estrous cycle affect experience-dependent plasticity in mouse primary visual cortexPLOS ONE Dear Dr. Gavornik, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please do follow useful directions to enhance the quality of your manuscript presentation. As soon as I received your response, I'll make final decision regarding your manuscript. Please submit your revised manuscript by Jan 26 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data. 4. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. 5. Please review your reference list to ensure that it is complete and correct. 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Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Rarely have I read a paper of such high quality. The writing is clear and concise, the data are analyzed with impeccable rigor, and the figure presentation is of the highest quality. The topic is of great importance, and the authors have done a very good job explaining the motivation for the study. They have set a high standard for the field. This will be a key reference text for all who study plasticity in the cerebral cortex. Reviewer #2: Overall, I think that the study was well designed, well written, and informative for designing future studies to examine potential cellular or molecular differences between cortical plasticity in male and female rodents. I do have a few comments for improving the manuscript. 1. Figure 2 would be easier to understand if the images were labeled with the estrous phase being shown. 2. In Figures 3 and 4 there is no indication of which groups are different which makes it difficult for the reader to follow. 3. It would be helpful to see the sample sizes indicated in the different figures. 4. Was data analyzed be repeated measures ANOVA? 5. Starting at line 270, it indicates there are some sex differences but there is no reference to the figure showing the difference. 6. Why did the female and male groups not differ in the sequence learning? Was this due to sample size or did difference in estrous cycle phase obscure differences compared to the male group? 7. The introduction to the sequential learning proposes that the sequential learning may be more sensitive to sex differences than the SRP. Was the sequential learning more sensitive? The normalized data showed no difference, but the raw data showed a sex difference. Was the difference due to starting from a different baseline or from less potentiation? Was the ratio of the response on the fifth day to the response on the first day greater in the males? 8. Do you think that that differences detected are large enough to cause functional differences? 9. Are the amplitudes of the VEP affected by the placement of the electrode or the size of the brain? ****** 6. 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Revision 1
31 Jan 2023 Author Response Responses to Journal Requirements: 1. Our revied manuscript carefully follows the style guide. 2. This work was funded by two NIH grants, one from NIMH and one from the NEI. Neither institute had a role in study design, etc. nor did they pay salary. Here is the funding statement: This work was funded by grants NIMH R00MH099654 and NEI R01EY030200. Neither institute took part in study design, data collection, or analysis or paid author salary. 3. Data not shown statements been removed from the paper. All data used for statistics, including both raw and normalized data, is available online via a link in the manuscript. 4. Our study did not use human subjects and needs no IRB approval or consent forms. The manuscript already includes details of our IACUC approved protocols. 5. Our reference list is correct. Responses to Reviewer’s Comments: Reviewer 1: We appreciate viewer 1’s enthusiastic support for this work. Reviewer 2: 1. Good suggestion, figure 2 has been modified. 2. The statistical details are included in the text, but at the reviewer’s suggestion we have also added indicators marking statistical difference to figures 3 and 4 and have also modified the figure legend to indicate significant differences. 3. Statistics, including n values, are reported in the text for all data. Following the reviewers comment we also added them to plot legends in figures 1, 3 and 4. 4. From the methods section: “Unless otherwise noted, 2-way ANOVAs were used to determine the statistical impact or either sex or estrus stage on stimulus evoked VEP potentiation as a function of either training day or stimulus type and the Shapiro-Wilk test was used to confirm data normality.” 5. For simplicity, in cases where normalized and raw data lead to the same statistical conclusions figure showed only the normalized plots. The average relative magnitudes of raw voltage traces can be seen on the voltage plots and all data (raw and normalized) are available for download from the repository cited in the paper. At the reviewer’s suggestion we added an explicit reference to figure 3C where significant day 5 differences are shown. 6. There is a small difference between male and female mice in sequence learning. The data shows that visual sequences drive slightly larger VEP responses in male populations than females, and that this difference accounts for the statistical effect found between the groups when calculated with raw (but not normalized) data. The details of this difference are included in the manuscript. 7. The difference between male and female mice found for raw voltages (see above) suggests sequence learning is more sensitive, but the 2-day induction experiment does not show increased sensitivity to estrous cycle. Overall the differences are small and can be controlled via normalization. The ratio of day 5 to day 1 was slightly larger in males (2.47x vs 2.38x) but this was not a large enough difference to make a statistical difference with normalized data. 8. Generally, no. The physiological differences are small enough that any functional dimorphism would likely be essentially de minimis. Confirming this with functional behavioral assays is beyond the scope of this work. 9. VEP morphology changes in a characteristic manner with electrode depth. Electrodes were placed at the same depth relative to the cortical surface in all mice which was confirmed via postmortem histology. Attachments Attachment Submitted filename: Response to Reviewers_2.pdf https://doi.org/10.1371/journal.pone.0282349.r002
14 Feb 2023 Decision Letter - Dragan Hrncic, Editor Sex and estrous cycle affect experience-dependent plasticity in mouse primary visual cortex PONE-D-22-27303R1 Dear Dr. Gavornik, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Prof. Dr. Dragan Hrncic Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0282349.r003
Formally Accepted
20 Feb 2023 Acceptance Letter - Dragan Hrncic, Editor PONE-D-22-27303R1 Sex and estrous cycle affect experience-dependent plasticity in mouse primary visual cortex Dear Dr. Gavornik: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Dragan Hrncic Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0282349.r004

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