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Blogging on Peer-Reviewed ResearchIt always feels good to report that one of one's own papers has been accepted for publication. This one has been in the works for a very long time and I'm especially happy that it's now finally coming out. The paper is entitled: "Double Dissociation of PKC and AC Manipulations on Operant and Classical Learning in Drosophila"
Actually, these data are a case study in how science publishing works today. I've tried and submitted several different versions to various open and closed access journals. I got pretty far in PLoS Biology, but one of the referees only liked the data, but didn't like the way the manuscript was written, so it was rejected. I admit, I had a lot of data and references in it, I always felt (and still do) this was the way papers should be: comprehensive and well-referenced. Maybe it was too unweildy. You go and judge it, I put this failed attempt on Nature Precedings in September last year. After that experience I thought I'd make it really, really short, give it a sexy title and avoid using the standard nomenclature in order to both appeal to a general audience as well as sound like I'm founding a new field (hey, something similar had worked for our Science paper). I got the manuscript ready, really liked the result and submitted it to Nature. It was rejected before review, so I put that failed version also on Nature Precedings (November). Finally, David Glanzman from UCLA saw the data on one of my posters at a Gordon Conference. He felt the data very convincing but too complex and too provokative and suggested to split the data into two papers. This was also the occasion for his legendary lecture on how paper writing is like a bull-fight smile.png. I did as he said and tried to write the first set of the data into a small, inconspicuous little paper and submitted it to Current Biology, where it now has finally appeared. I will be eternally grateful for David's advice.

The paper describes experiments showing that operant conditioning and classical conditioning have two different genetic bases and that classical learning dominates operant learning if both classical and operant predictors are available. Here's the abstract of the paper entitled "Double Dissociation of PKC and AC Manipulations on Operant and Classical Learning in Drosophila":
Learning about relationships between stimuli (i.e., classical conditioning) and learning about consequences of one's own behavior (i.e., operant conditioning) constitute the major part of our predictive understanding of the world. Since these forms of learning were recognized as two separate types 80 years ago, a recurrent concern has been the issue of whether one biological process can account for both of them. Today, we know the anatomical structures required for successful learning in several different paradigms, e.g., operant and classical processes can be localized to different brain regions in rodents and an identified neuron in Aplysia shows opposite biophysical changes after operant and classical training, respectively. We also know to some detail the molecular mechanisms underlying some forms of learning and memory consolidation. However, it is not known whether operant and classical learning can be distinguished at the molecular level. Therefore, we investigated whether genetic manipulations could differentiate between operant and classical learning in Drosophila. We found a double dissociation of protein kinase C and adenylyl cyclase on operant and classical learning. Moreover, the two learning systems interacted hierarchically such that classical predictors were learned preferentially over operant predictors.
There are  a few reasons why I am particularly excited about these findings. The first one is that they suggest that the 80-year-old procedural distinction between operant and classical learning is not reflected in the biologial learning processes in the brain at all. It is not only the procedure of how the animal learns something that is critical, but especially what it learns. The operant/classical distinction says nothing about what is learned and as such is not of much use for biological studies. The second is that there seems to be a complete separation between the AC-dependent Pavlovian processes and the PKC-dependent behavioral learning processes, with defined interactions between the two mechanisms. On top of that, my old lab in Houston, Texas has just now found out that PKC is also involved in operant learning in the marine snail Aplysia. Their research will appear in September in the journal Neuron. This coincident finding raises the possibility that just like synaptic plasticity, the PKC-dependent mechanism - whatever it may turn out to be - may also be evolutionary conserved from snails and flies to mammals.
If this were indeed the case, there would be a whole new field of learning research opening up. This field would be especially pertinent for all drug-addiction research, because there are now are several lines of evidence (also fom Aplysia and flies) that the PKC-dependent mechanism is probably the one involved in habit formation. One of my favorite scenarios I fantasize about is to add a very specific PKC-inhibitor to drugs of abuse so we can all get high but never get addicted stonedagain.png This is probably an oversimplification, but it's a good answer when people ask me what I do for a living smile.png. Now, if that piqued your curiosity, you can go and read our explanation of the paper in lay terms, richly illustrated with videos and figures.

Posted on Thursday 31 July 2008 - 19:06:22 comment: 0
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