Dear Dr. Lazar,

Thank you very much for submitting your manuscript "The functional logic of odor information processing in the Drosophila Antennal Lobe" for consideration at PLOS Computational Biology.

As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. 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.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

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

Sincerely,

Alexandre V. Morozov, Ph.D.

Academic Editor

PLOS Computational Biology

Wolfgang Einhäuser

Section Editor

PLOS Computational Biology

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Reviewer's Responses to Questions

Comments to the Authors:

Reviewer #1: The review is uploaded as an attachment

Reviewer #2: My review is uploaded as an attachment

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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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.

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Reviewer #1: No

Reviewer #2: Yes: Alexander Shakeel Bates

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that 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 to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: flyAntennalLobe_review.pdf

Attachment

Submitted filename: plos_comp_#1.docx

Dear Dr. Lazar,

Thank you very much for submitting your manuscript "The Functional Logic of Odor Information Processing in the Drosophila Antennal Lobe" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. 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

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

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

Sincerely,

Alexandre V. Morozov, Ph.D.

Academic Editor

PLOS Computational Biology

Wolfgang Einhäuser

Section Editor

PLOS Computational Biology

***********************

A link appears below if there are any accompanying review attachments. If you believe any reviews to be missing, please contact ploscompbiol@plos.org immediately:

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: Review comments are in the attachment

Reviewer #2: I thank Lazar and colleagues for their work in addressing my concerns and those of reviewer 1. In particular, in improving the readability of the manuscript. Having now read comments from reviewer 1, the authors’ rebuttal and their revised manuscript I would like to re-hash one of my prior opinions rather strongly. I will not require that it needs be addressed for the paper to proceed - but I very strongly recommend to the authors that it should be, in service to the utility and impact of their work at a time for the field where linking mechanism and computation to identified neuronal hardware has never been easier and more fruitful.

I am not convinced by the authors’ claim that they do not need to consider available connectome data in this work. Reviewer 1 suggested using the connectome very broadly, and the authors replied that this was not in scope. I agree with them on that front, but a simple connectome analysis should be done to at the very least contextualise their work. I raised this point strongly in my first review, and the authors essentially ignored it. In response to my points on connectome, anatomy, and prior literature, the authors did not answer my questions but told me that they are coming at the problem from a computational logic/theory point of view, and so use abstractions inspired by the systems neuroscience view but not necessarily linked to it. I understand this perfectly well and do not take issue with any of their abstractions - yet: there is no point in describing an abstract computation for the fly antennal lobe if the fly antennal lobe does not contain the wetware to run it. Indeed, figures 3 and 4 show model architectures that can be directly linked to the neurobiological network diagram - it is a small step!

The paper is about how the fly olfactory system - not something more abstract than that - and is based on anatomical connections observable within that system. The biological constraints are important. Very important, and the easier constraints to understand come from network structure - the authors have already tried hard in the more difficult case of neurophysiology. I am not asking the authors to use connectome-derived weights or exact neuron identities in their work, or build any kind of mechanistic model. Nor am I asking for a higher level characterisation of the network in terms of feedback loops and similar, as they present in another of their bioRxiv papers that they reference (rebuttal reference 3). Rather, it is totally in keeping with the nature of the work at hand to ask whether the motifs Lazar et al. are studying actually exist and in what proportions, and to what identified cell types they pertain - none of this is dealt with in reference 3. The latter point is instrumental in providing a starting point for experimentation that might validate some of this modelling work. I am asking for a simple descriptive summary - in its simplest form, this might be some histograms or stacked bar plots showing the incidence of pre/post i/e LN-OSN connectivity. This is not about a clash of perspectives, it is about integration. To do otherwise at this time in the field is to knowingly limit the impact and usability of this work. To be clear again, I am not asking them to change anything about how their modelling is done. It is context I am after.

For example, does the connectome contain neurons that can be arranged as required for the authors’ DNPs? How frequently do you find pre-LN, post-iLN and post-eLN innervation patterns, and does this differ between glomeruli? Do eLN-OSN inputs exist at all, or are they not important? Reviewer 1 also asked why the authors “eliminate presynaptic excitatory LNs to the terminal of OSN axons”. I found the authors’ reply, essentially that they did not need to, lacking. It is a clear and singular complement to the motifs they have already chosen. Its absence is conspicuous. Are there excitatory LN inputs to OSN axons in the fly brain? The authors say they ‘we believe that, algorithmically, it is beneficial for the LN pathways to process syntactic information and semantic information independently.’ Does this pathway separation anatomically exist?

The sum of my point here is: the authors put a lot of weight into trying different network configurations and showing us and explaining the model architecture and its operations but none into telling us - given the open source data available to them via Scheffer et al. and the annotations from Schlegel et al. - whether the fly has the neuronal architectures to support it.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: None

Reviewer #2: Yes

**********

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 #1: No

Reviewer #2: Yes: Alexander Shakeel Bates

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that 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 to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References:

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 rebuttal letter that accompanies your revised manuscript.

If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Attachments

Attachment

Submitted filename: flyAntennalLobe_review.pdf

Dear Dr. Lazar,

We are pleased to inform you that your manuscript 'The Functional Logic of Odor Information Processing in the Drosophila Antennal Lobe' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Alexandre V. Morozov, Ph.D.

Academic Editor

PLOS Computational Biology

Wolfgang Einhäuser

Section Editor

PLOS Computational Biology

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