Björn Brembs

[*During my [flyfishing vacation last
year](http://blogarchive.brembs.net/comment-n862.html), pretty much
nothing was happening on this blog. Now that I've migrated the blog to
WordPress, I can actually schedule posts to appear when in fact I'm not
even at the computer. I'm using this functionality to re-blog a few
posts from the [archives](http://blogarchive.brembs.net) during the
month of august while I'm away. This post is from [April 28,
2011](http://blogarchive.brembs.net/news734.html):  
*]{style="font-size: 12px;"}

<div>

It turns out, [operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"} is very different from other forms of learning, all the
way from the genes up. When I started my research on [operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"} in 1995, I did so with the opposite hypothesis, namely
that the underlying mechanism of all learning processes was always
[synaptic
plasticity](https://en.wikipedia.org/wiki/Synaptic_plasticity){target="_blank"
rel="external"} with the well-known molecular pathway: Ca^++^, cAMP,
PKA, CamK, CREB and so on. After all, wasn't that pathway conserved all
the way from flies, snails and mice to humans? By the time I finished by
PhD in 2000, [Eric
Kandel](https://en.wikipedia.org/wiki/Eric_Kandel){target="_blank"} had
received the Nobel prize for exactly these learning mechanisms -- he
wouldn't have gotten the prize if the pathways had not been so
conserved. In principle, changing the weight of the synapses is all you
need to do to store whatever information you want. There is no a priori
need to have several different mechanisms by which neural networks are
modified.

</div>

A few years ago, I started getting data from fruit flies (
*[Drosophila](http://brembs.net/learning/drosophila/){target="_blank"
rel="external"}*) that were exactly the opposite of what my initial
hypotheis was: the genes required for standard synaptic plasticity (such
as the [*rutabaga*](https://en.wikipedia.org/wiki/Rutabaga_%28gene%29)
adenylyl cyclase) were not required in our form of [operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"}. In contrast, a gene which had previously been shown not
to be involved in [classical
conditioning](http://brembs.net/learning/classical.html){target="_blank"
rel="external"}, protein kinase C (PKC) turned out to be crucial for
[operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"}. What made the whole story even more intriguing was that
the same evidence started to show up in the lab where I did my postdoc,
using the marine snail
*[Aplysia](http://brembs.net/learning/aplysia/){target="_blank"
rel="external"}* as a model system: PKC was required, but the
*rut*-cyclase was not.

Why had nobody discovered this dichotomy between the learning mechanisms
before us? It turned out that the crucial experimental advance was to
prevent the animals from learning about anything else besides their
behavior. As soon as we let the animals learn about any external cues in
addition to their behavior, the results go back to the expected
canonical pathways being required and PKC not. Obviously, nobody had
been able to completely isolate [operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"} to the extent that was required. Because all our
experiments were operant in nature, but only differed in whether or not
the animals were able to learn about environmental cues or not, we
called the PKC-dependent learning mechanism operant self-learning and
the other, well-described form, operant world-learning.

How far is this new form of plasticity (in
*[Aplysia](http://brembs.net/learning/aplysia/){target="_blank"
rel="external"}* it is a form of 'intrinsic plasticity' modifying the
entire neuron and not just the synapse; in
*[Drosophila](http://brembs.net/learning/drosophila/){target="_blank"
rel="external"}* we don't know) conserved? We are currently in the
process of writing up our experiments on the 'language gene'
[FoxP2](https://en.wikipedia.org/wiki/FOXP2){target="_blank"}.
*[Drosophila](http://brembs.net/learning/drosophila/){target="_blank"
rel="external"}* has an orthologue of this gene and if we mutate it (or
knock it down with RNAi), we find that it is required for operant
self-learning, but not for operant world-learning, paralleling the
results we had for PKC. This means we now have a new learning mechanism
at hand that is clearly distinct from the well-known synaptic plasticity
pathway, but is equally conserved among invertebrates and vertebrates.
These results suggest an ancient evolutionary origin for operant
self-learning, possibly at the root of the bilaterian branch, and a
complementary role to world-learning.

I have summarized these results in an [invited
review](https://dx.doi.org/10.1016/j.beproc.2011.02.005) on occasion of
the 2010 conference of [SQAB](https://www.sqab.org/){target="_blank"} in
the journal "Behavioural Processes". Unfortunately, there are a few
mistakes in the copy available from the publisher. Some spaces are
missing between words and the references Brembs 2009a and Brembs 2009b
are mixed up. I've notified the publisher, but they said it was too late
to fix. I've now fixed the [HTML version of my local
copy](http://brembs.net/learning/drosophila/behavproc11/index.html){target="_self"},
but I can't fix [my PDF
copy](http://blogarchive.brembs.net/request101.html){target="_self"} as
they use a font that is not freely avaliable. So if anybody knows how I
can fix my own PDF copy, please let me know!

------------------------------------------------------------------------

<div>

Brembs, B. (2011). Spontaneous decisions and [operant
conditioning](http://brembs.net/learning/operant.html){target="_blank"
rel="external"} in fruit flies Behavioural Processes DOI:
[10.1016/j.beproc.2011.02.005](https://dx.doi.org/10.1016/j.beproc.2011.02.005){rev="review"}

</div>


<em>
 During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away.
</em>

Publicaciones de Rogue Scholar

Flashback: The neurobiology of operant conditioning