This is the first installment of what will be an ongoing series of capsule summaries of the Shea Lab journal club meetings. We are doing this to actively provoke open discussion of papers we read that are either published in a traditional journal or BioRxiv.
This meeting was attended by members of the Shea and Tollkuhn labs. Names have been changed to protect the opinionated 🙂
Dang, this is one big, hairy beast of a paper! It starts out with a pretty straightforward and very important goal: to develop a sensitive and selective antibody to the mouse receptor for the neuromodulator oxytocin and identify the pattern of expression at the regional circuit and sub cellular levels. The paper does that rather nicely and then goes on to incorporate EM, RNAseq, and in vitro and in vivo electrophysiology over the course of 13 figures.
Like I said, the first half of the paper is a tight and thorough execution of the goal as formulated above. The authors identify for the first time the network of brain regions that express this receptor, and they observe a provocative pattern of presynaptic expression that was (to me anyway) unexpected. They achieve this by bearing down on the formidable task of developing and validating an OXTR antibody
The second half of the paper runs through an series of exciting but somewhat preliminary observations primarily using in vitro and in vivo electrophysiology. Most of this stuff is super interesting, examining oxytocin’s acute neuromodulatory effects and its effects on synaptic plasticity. The down side is that many of these effects are not deeply explored, so I hope that they get followed up on. A little bird told me that a lot of these things were responses to reviewer comments, which is weird to me. It seems to me that the physiology would be better served in its own venue. Greedy reviewers!
Strengths/Praise: All present agreed that the paper’s greatest contribution was the development of a high quality antibody for oxytocin and the visualization of the brain-wide expression pattern. The apparent rigor with which this was done is a major strength. These resources provide an important substrate for future work.
Secondary, but also important, is the fact that this paper avoids the media glam image of oxytocin as a “love molecule” and takes it seriously as a modulator of neuronal activity and plasticity.
There were other nuggets of interest. The motif of presynaptic expression suggests some interesting unexpected functions for oxytocin. Also, the fact that OXT+ fibers overlapped the OXTR+ cells in certain hypothalamic regions but not elsewhere suggested to me distinct, circuit-specific modes of point-to-point and volume transmission. But that’s probably speculative of me.
Weaknesses/Criticism: Our major criticism was that the paper could have ended after 7 or 8 figures and started a new paper. But like I said, I subsequently learned that these were things the reviewers asked about, so maybe we shouldn’t fault the authors.
One other minor critique that came up was that the authors may have been a bit chauvinistic in choosing the regions they focused on. The auditory cortex is not one of the top expressing regions based on raw cell count, The counter argument I suppose is that with this kind of staining, sparse does not always imply weak. Also, looking at the auditory cortex is well motivated by a recent high profile study by this group.