Decision letter | Recognition of familiar food activates feeding via an endocrine serotonin signal in Caenorhabditis elegans

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Recognition of familiar food activates feeding via an endocrine serotonin signal in Caenorhabditis elegans

Decision letter

Peggy Mason, Reviewing editor, University of Chicago, United States

eLife posts the editorial decision letter and author response on a selection of the published articles (subject to the approval of the authors). An edited version of the letter sent to the authors after peer review is shown, indicating the substantive concerns or comments; minor concerns are not usually shown. Reviewers have the opportunity to discuss the decision before the letter is sent (see review process). Similarly, the author response typically shows only responses to the major concerns raised by the reviewers.

Thank you for choosing to send your work entitled “Recognition of familiar food activates feeding via an endocrine serotonin signal in C. elegans” for consideration at eLife. Your article has been evaluated by a Senior editor and 3 reviewers, one of whom is a member of our Board of Reviewing Editors. Peggy Mason served as the Reviewing editor.

The Reviewing editor and two reviewers discussed their comments before we reached this decision, and the Reviewing editor has assembled the following comments based on the reviewers' reports.

Your work is thorough, interesting, and novel. Attention to the following points would further strengthen the manuscript:

* Not all pairwise combinations are tested in behavioral assays with HB101 always being tested against one of the others. The consistency of the behavioral results mitigates this concern but the lack of a second comparison is more problematic in the Ca++ imaging study.

* Is it possible to elicit pharyngeal pumping by ADF activation?

* Day-to-day variations in feeding rates are as large or larger than the familiarity effect. Depending on how the experiments were done, this could be of serious concern or simply puzzling. It should be stated explicitly whether experiments and controls for every comparison were done on the same day, using the same reagents. The variability in baseline pumping rate appears as an issue in much of the data and is of particular concern with regard to drawing negative conclusions (e.g., Figure 5a, Figure 8c–d).

* What were the actual values of R, i.e., of the exponential fit of the baseline I535/I480 ratio and their variations? Do ADF::gfp animals display similar rates of bleaching? The average values of the individual yellow and cyan channels should also be presented. A description of the design of the microfluidic chip (or a reference) should be given. How much time passed from picking to imaging?

[Editors' note: the following comments were sent to the authors upon evaluating the revised manuscript.]

One issue that still concerns us is the day-to-day variation issue. Of course we understand that variation happens. At the same time, the range of the day-to-day variation (about 100 pumps/min) is larger than the size of the effect (about 20). Your response mentions that you always tested worms in two conditions at the same time, and on the same day with the same reagents. Then you state that you combined data from 3–5 experiments (meaning 3–5 days presumably) together. This latter methodology makes the variability more difficult to understand. Why wouldn't the day-to-day variation average out similarly across groups? Moreover, if similar numbers of experiment- and control-animals were not assayed in each experiment, then how can data from the different days be grouped together (unless there was no day-by-day variation)? It is therefore necessary to provide more methodological details. Finally, related to this issue are negative conclusions from experiments that have control pumping rates on the very low side (e.g., Figures 4b, 5a). As it is not clear that the pumping rate could be lower than such low control values, it is not clear that the conclusions stated are warranted.