From Figure 1, Li et al.

I wanted the title of this post to be “A tale of two one two three papers” but I couldn’t figure out how to get strikethroughs in the title field. And I thought “A tale of two, make that one, no make that two again, oops now three” might be a bit cumbersome. As promised, here’s another installment of the discussion of what happens when we receive conceptually related/overlapping papers. It starts with a paper that appeared just yesterday in Neuron by Kenichi Ohki and colleagues describing how mouse visual cortex neurons that developed from the same neural progenitor cell tend to be more similar functionally than those that did not.

Why is this significant? First a little background. Cells in visual cortex are tuned to different aspects of visual stimuli, such as orientation or direction, and anatomically are organized quite specifically. Cells with similar preferences tend to cluster together and to be selectively connected with each other (though to differing degrees in different species), and this specificity may underlie some of the many computations required to turn photons of light hitting our eyes into comprehensible percepts.  It’s been proposed that this clustering could start in early development; neurons born from the same neural progenitor migrate vertically to form columns of sibling neurons, and could be the basis for clusters of adult cells with similar properties. That link hasn’t been demonstrated experimentally until now, and Ohtsuki et al. provides some evidence in support of it.

Now, visual cortex aficionados among you may think this sounds a bit similar to Li et al., a paper by Yang Dan and colleagues that appeared a few months ago, and indeed it is. And you may also recall that THAT paper appeared alongside Yu et al. from Songhai Shi’s lab about the development of synapses between sibling neurons.

So here’s the story from the beginning (or rather, the beginning of our involvement with the manuscripts).

We first received Yu et al., which concerns how sibling neurons in cortex preferentially form electrical synapses (gap junctions) early in development and the consequences this early gap junction signaling has for the formation of specific chemical synapses later. “Interesting but thin,” we thought when making our initial assessment to review, “wouldn’t it be nice if the authors could demonstrate some functional consequences?” We then received Li et al. showing just that; they found that sibling neurons are more similar functionally, and if you block gap junctions early in development, that increased similarity goes away. “Interesting” we thought (again) “but a bit thin.”  Since one of the authors was on both papers, our next thought was, “Aha! together these would make one amazing paper.” So we approached the reviewers and the authors about the idea of combining the two into a single paper. And we were most politely but firmly dissuaded from the notion.  What persuaded us was not just the conceptual advance offered by each individual paper, but also the human factor. These were independent projects done in different labs, with different first authors who deserved credit for their work. We switched our focus to what the reviewers felt they needed to see in order to be persuaded of the robustness of the individual conclusions, and were happy to accept both for publication after some revisions.

This is the point in the story where the Neuron paper enters, the one with highly overlapping conclusions to Li et al. The authors of the Ohtsuki et al. have graciously granted us permission to divulge that their paper was first submitted to us and that we had to decline it (we wouldn’t reveal this information otherwise). Our editorial assessment was that (obviously) the topic of the paper was interesting, and that the work appeared high quality, but that novelty was compromised. Even so, we did consider giving it an expedited review given how close in time it followed, and because its conclusions did differ somewhat.  But, Li et al. contained additional parts to the story that Ohtsuki et al did not have, including manipulations to disrupt the sibling cell similarity (ie blocking gap junctions early in development) and additional characterization of multiple visual properties. In the course of our deliberations on the two Nature papers, we had determined that publication of Li et al. was conditional upon the authors strengthening those additional pieces of the story. So we felt it would not be consistent or fair to consider a paper that did not contain them, nor did we think it would be productive to ask the authors of Ohtsuki et al. for months’ more worth of work in this situation. We felt the best we could offer (in our pages) was a Brief Communications Arising once Li et al. had been published. Happily, the authors found another journal able to publish their paper on a relatively fast time frame and I’m glad to be able to present the whole package here today.

From Mrsic-Flogel & Bonhoeffer

If you want to read more about the science, I direct you to not one, but two, excellent commentaries: one in our pages by Tom Mrsic-Flogel and Tobias Bonhoeffer about the two Nature papers and one in Neuron by Gordon Smith and David Fitzpatrick. The Neuron commentary provides a great explanation of the similarities and differences between the studies (and suggests a couple of R01’s worth of future experiments). I highly recommend you check them out.

12/11/12: edited to fix typos – thanks to Steve Esterly for flagging