Decision letter | A cellular mechanism for inverse effectiveness in multisensory integration

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A cellular mechanism for inverse effectiveness in multisensory integration

Decision letter

Affiliation details

Brown University, United States; Bard College, Unied States; Roger Williams University, United States
Gary L Westbrook, Reviewing editor, Vollum Institute, United States

In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.

Thank you for submitting your article "A Cellular Mechanism for Inverse Effectiveness in Multisensory Integration" for consideration by eLife. Your article has been reviewed by two peer reviewers, and the evaluation has been overseen by Gary Westbrook as the Senior Editor and Reviewing Editor. The following individuals involved in review of your submission have agreed to reveal their identity: Barry Stein (Reviewer #1); Hollis T Cline (Reviewer #2).


The reviewers have discussed the reviews with one another and the Senior Editor has drafted this decision to help you prepare a revised submission. As you will see from their comments below, both reviewers thought that this was an excellent manuscript and an appropriate Research Advance to complement your recent eLife paper. Please include a response to each comment in your revised cover letter and adjust the text of the manuscript to address each comment.

Reviewer #1:

This is a straightforward demonstration that a well-known property of multisensory integration ("Inverse Effectiveness") is present in the nonmammalian homologue of the Superior Colliculus – the Optic Tectum. The authors have done a nice job of using multiple techniques to demonstrate its presence, its operational constraints, its likely molecular basis, as well as its physiological and behavioral manifestations in Xenopus tadpoles. There are a few suggested changes for clarity.

1) It is interesting that the authors use the term "conserved" for the presence of Inverse Effectiveness. Presumably, they are assuming that the progenitor of amphibians and mammals had this property – although this is not stated. It is, of course, possible that it was invented and re-invented in different species. Also, the description in the text gives the impression that the authors think it has been conserved from mammalian forms. Clearly, this is not what they mean. One might say that it is actually conserved in more recent beasts (i.e., mammalians).

2) Including the behavior of the animal is really a good idea, because it shows that this physiological property is reflected in overt responses. It should be noted that a similar strategy had previously been used for similar reasons (see Stein et al. 1988, 1989 – cat behavior).

3) Is there confidence that the "acoustic" stimulus was activating the auditory system and not the vibratory (i.e., tactile) system (since the presence of the stimulus was judged by the vibration of the liquid in which the animals were swimming)?

4) Mechanosensory is the assumption the authors have for this stimulus – but, it is an electrical stimulus, not a mechanical one. As such, it could be activating any component of the somatosensory system – cutaneous, deep, nociceptive, etc. "Electrical stimulation of the skin" might a better descriptor.

5) Two different combinations of stimuli were used for testing different hypotheses (visual and "auditory", and visual (optic chiasm stimulation) and "mechanosensory". This was done for convenience and presumably there is no difference here in how the different modality combinations work, but a statement should be made somewhere as to why this was done (for convenience is fine).

Reviewer #2:

This paper examined the cellular basis for inverse effectiveness, a feature of multisensory integration, using Xenopus tapdoles. The authors use behavior, electrophysiological recordings and calcium imaging to examine the mechanisms underlying inverse effectiveness. They demonstrate that pairing auditory startle stimulus with weak visual input produces a stronger behavioral output (change in swim speed) that pairing the auditory input with weak stimulus, indicative of multisensory integration. They use calcium imaging to characterize neurons that are multisensory and show inverse effectiveness. They show that inverse effectiveness is not blocked by picrotoxin but is blocked by NMDA R. This study is beautifully conducted, and provides important cellular level resolution of the mechanisms underlying an important aspect of multisensory integration. I find no flaws with the manuscript, and only a single comment as below:

1) There is no need to abbreviate inverse effectiveness.