Dear Dr Radwańska,

Thank you for submitting your manuscript entitled "Phosphorylation of PSD-95 at Serine 73 in dCA1 is required for extinction of contextual fear" for consideration as a Research Article by PLOS Biology.

Your manuscript, the Review Commons reviews and your point-by-point response has now been evaluated by the PLOS Biology editorial staff, as well as by an academic editor with relevant expertise. I am writing to let you know that we would like to send your revised submission out to the Review Commons reviewers for peer review at PLOS Biology.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

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Feel free to email us at plosbiology@plos.org if you have any queries relating to your submission.

Kind regards,

Kris

Kris Dickson, Ph.D., (she/her)

Neurosciences Senior Editor/Section Manager

PLOS Biology

kdickson@plos.org

Dear Dr Radwańska,

Thank you for your patience while your revision plan to your Review Commons submission "Phosphorylation of PSD-95 at Serine 73 in dCA1 is required for extinction of contextual fear" was reviewed by the PLOS Biology editors, and Academic Editor and one of the original Review Commons reviewers (Reviewer 2). We would like to invite you to revise the work to thoroughly address the reviewers' reports as you have outlined. Please note that Reviewer 2 also requests some additional electrophysiology work that we would also like to see you incorporate.

Given the extent of revision needed, we cannot make a decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript will be sent for further evaluation by the original Review Commons reviewers when it is resubmitted.

We expect to receive your revised manuscript within 3 months. Please email us (plosbiology@plos.org) if you have any questions or concerns, or would like to request an extension.

At this stage, your manuscript is under active consideration at our journal; please notify us by email if you do not intend to submit a revision so that we may withdraw it.

**IMPORTANT - SUBMITTING YOUR REVISION**

Your revisions should address the specific points made by each reviewer during the Review Commons review process, along with the additional comments raised by Reviewer 2 below. Please submit the following files along with your revised manuscript:

1. A 'Response to Reviewers' file - this should present a point-by-point response to all of the reviewers' comments (both original Review Commons and ones below), and indicate the changes made to the manuscript.

*NOTE: In your point-by-point response to the reviewers, please provide the full context of each review from Review Commons and from below. Do not selectively quote paragraphs or sentences to reply to. The entire set of reviewer comments should be present in full and each specific point should be responded to individually, point by point.

You should also cite any additional relevant literature that has been published since the original submission and mention any additional citations in your response.

2. In addition to a clean copy of the manuscript, please also upload a 'track-changes' version of your manuscript that specifies the edits made. This should be uploaded as a "Revised Article with Changes Highlighted" file type.

*Re-submission Checklist*

When you are ready to resubmit your revised manuscript, please refer to this re-submission checklist: https://plos.io/Biology_Checklist

To submit a revised version of your manuscript, please go to https://www.editorialmanager.com/pbiology/ and log in as an Author. Click the link labelled 'Submissions Needing Revision' where you will find your submission record.

Please make sure to read the following important policies and guidelines while preparing your revision:

*Published Peer Review*

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. Please see here for more details:

https://blogs.plos.org/plos/2019/05/plos-journals-now-open-for-published-peer-review/

*PLOS Data Policy*

Please note that as a condition of publication PLOS' data policy (http://journals.plos.org/plosbiology/s/data-availability) requires that you make available all data used to draw the conclusions arrived at in your manuscript. If you have not already done so, you must include any data used in your manuscript either in appropriate repositories, within the body of the manuscript, or as supporting information (N.B. this includes any numerical values that were used to generate graphs, histograms etc.). For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5

*Blot and Gel Data Policy*

We require the original, uncropped and minimally adjusted images supporting all blot and gel results reported in an article's figures or Supporting Information files. We will require these files before a manuscript can be accepted so please prepare them now, if you have not already uploaded them. Please carefully read our guidelines for how to prepare and upload this data: https://journals.plos.org/plosbiology/s/figures#loc-blot-and-gel-reporting-requirements

*Protocols deposition*

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for your submission to our journal. We hope that our editorial process has been constructive thus far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Kris

Kris Dickson, Ph.D., (she/her)

Neurosciences Senior Editor/Section Manager

PLOS Biology

kdickson@plos.org

------------------------------------

REVIEWS:

Reviewer's Responses to Questions

Do you want your identity to be public for this peer review?

Reviewer #1: Yes: Kim Dore (Originally Reviewer 2 at Review Commons)

Reviewer #1: I reviewed this manuscript for Review Commons (I'm reviewer #2).

The authors responded to my comments in the response letter by saying that they will do all the requested changes and one other experiment I requested (regarding Fig. 6, third comment). If the authors are indeed making all the requested changes, I think this publication would be of interest to PLOS biology readers.

One thing I'm unsure about is the answer to the first 'major point' I noted. I'm still very concerned about the effects of WT-PSD-95 expression on learning and memory as it's been shown in vitro that it blocks LTP and enhance LTD.

Even if overpexpression leads to 'only' a 40% increase in PSD-95 in vivo, I would expect it to have an impact on synaptic plasticity. A great way to test this would be to do electrophysiology on acute slices made from control or injected animals.

If LTP can be induced in PSD-95 injected animals, that would support the results presented and confirm that memory formation is intact in these animals.

I look forward to see how the authors will address all the comments in the revised manuscript.

Dear Dr Radwańska,

Thank you for your patience while we considered your revised manuscript "Phosphorylation of PSD-95 at Serine 73 in dCA1 is required for extinction of contextual fear" for publication as a Research Article at PLOS Biology. This revised version of your manuscript has been evaluated by the PLOS Biology editors and the Academic Editor, who feels the manuscript has properly addressed the reviewer comments.

Therefore, based on our Academic Editor's assessment of your revision, we are likely to accept this manuscript for publication. However, before we can editorially accept your study, we need you to address the following data and other policy-related requests in a revised manuscript that we think should not take very long.

**EDITORIAL REQUESTS:

1) TITLE: We think that 'Serine' should not be capitalized in the title. If you agree, we suggest you change the title to: "Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear"

2) FINANCIAL DISCLOSURES: Please update your financial disclosures statement to describe the role of any sponsors or funders in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. If the funders had no role in any of the above, include this sentence at the end of your statement: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

3) DATA REQUEST: Thank you for including the raw western blot images related to your manuscript. Can you please annotate this data, to clearly indicate which figure panel the image corresponds to, to note the loading order, antibody used, and molecular weights? Please add these annotations without obscuring the lanes. Please carefully read our guidelines for how to prepare and upload this data: https://journals.plos.org/plosbiology/s/figures#loc-blot-and-gel-reporting-requirements

4) DATA REQUEST: Thank you also for uploading the raw data underlying your figures on OSF. Can you please reference this dataset in each figure legend? For example, to each figure legend (including supplemental figure legends), you can add the sentence "the data underlying this figure is available from OSF (https://osf.io/cgfa9/)

5) ABSTRACT: Please note that per journal policy, the model system/species studied should be clearly stated in the abstract of your manuscript. Please update it accordingly.

As you address these items, please take this last chance to review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the cover letter that accompanies your revised manuscript.

We expect to receive your revised manuscript within two weeks.

To submit your revision, please go to https://www.editorialmanager.com/pbiology/ and log in as an Author. Click the link labelled 'Submissions Needing Revision' to find your submission record. Your revised submission must include the following:

- a cover letter that should detail your responses to any editorial requests, if applicable, and whether changes have been made to the reference list

- a Response to Reviewers file that provides a detailed response to the reviewers' comments (if applicable)

- a track-changes file indicating any changes that you have made to the manuscript.

NOTE: If Supporting Information files are included with your article, note that these are not copyedited and will be published as they are submitted. Please ensure that these files are legible and of high quality (at least 300 dpi) in an easily accessible file format. For this reason, please be aware that any references listed in an SI file will not be indexed. For more information, see our Supporting Information guidelines:

https://journals.plos.org/plosbiology/s/supporting-information

*Published Peer Review History*

Please note that you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. Please see here for more details:

https://blogs.plos.org/plos/2019/05/plos-journals-now-open-for-published-peer-review/

*Press*

Should you, your institution's press office or the journal office choose to press release your paper, please ensure you have opted out of Early Article Posting on the submission form. We ask that you notify us as soon as possible if you or your institution is planning to press release the article.

*Protocols deposition*

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please do not hesitate to contact me should you have any questions.

Sincerely,

Luke

Lucas Smith, Ph.D.

Associate Editor,

lsmith@plos.org,

PLOS Biology

Dear Dr Radwańska,

Thank you for the submission of your revised Research Article "Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear" for publication in PLOS Biology. On behalf of my colleagues and the Academic Editor, Eunjoon Kim, I am pleased to say that we can in principle accept your manuscript for publication, provided you address any remaining formatting and reporting issues. These will be detailed in an email you should receive within 2-3 business days from our colleagues in the journal operations team; no action is required from you until then. Please note that we will not be able to formally accept your manuscript and schedule it for publication until you have completed any requested changes.

Please take a minute to log into Editorial Manager at http://www.editorialmanager.com/pbiology/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process.

PRESS

We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with biologypress@plos.org. If you have previously opted in to the early version process, we ask that you notify us immediately of any press plans so that we may opt out on your behalf.

We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

Thank you again for choosing PLOS Biology for publication and supporting Open Access publishing. We look forward to publishing your study. 

Sincerely, 

Lucas Smith, Ph.D.

Associate Editor

PLOS Biology

lsmith@plos.org