Saturday, January 30, 2010

Nobel Winner's Curse

Bert Sakmann visited Duke last Friday to give a seminar on his current work (streaming video here).  By my count, he is the sixth Nobel prize winner I have seen speak.  Three of them (Roger Tsien, Eric Kandel, and Torsten Wiesel) gave overviews of their important works, appropriate to the large audiences they were speaking before.  The other three (Richard Axel, Bert Sakmann, and Susumu Tonegawa) spoke about the current research in their labs, and largely neglected what made them famous.  From their perspective, like a famous rock band, they must decide between playing the audience's favourite songs, or playing the new songs, which while potentially not as good, are what they care about now.

Bert Sakmann is most famous for co-inventing the patch-clamp technique, which allows one to record the actual voltage of individual neurons in the brain.  The basics of the technique is that you take a microscopically thin glass cylinder, called a pipette, and bring it so close to the cell membrane that the membrane adheres to the pipette.  Ideally, this attachment is so strong that it creates a high electrical resistance, or gigaOhm seal.  While you are attached to a cell like this, you can indirectly measure the voltages of the cell.  However, to truly measure the cell voltage, you need direct access to the fluid inside the cell, which can be obtained by opening a hole in the membrane.  This is traditionally achieved by literally sucking on a tube connected to the pipette.  The idea that the fundamental technique of electrophysiology involves puncturing cells by sucking on a straw still tickles me.

Since inventing the whole cell patch technique, Sakmann, like many other famous scientists, has turned his direction "upwards" to more systems oriented questions.  The specific system he is now studying is the barrel cortex.  The barrel cortex is the part of a rodent's brain responsible for decoding what its whiskers are touching.  Each whisker is has a small portion of the cortex dedicated to it called a "barrel."

People have traditionally thought of cortex as having an hierarchical structure, where information flows into one layer, then proceeds through the six layers of cortex until being output not another area of the brain. This theory has come from extensive work in the visual cortex of rats, cats, and other mammals. Sakmann's group  recorded (using patch clamp!) from all of the layers of barrel cortex while stimulating the whiskers, and found that information reaches all layers of the cortex simultaneously, in contrast to visual cortex.  Previously, people have postulated that perhaps cortical columns (small vertically organized units of cortex covering all six layers) were a general processing unit that had been repeated with variation in different parts of the cortex.  By showing that barrel cortex works differently, systems neuroscientists must now be more careful in how the think about information flow. (I should also say at this point that I am not a systems neuroscientist, and do not have a firm knowledge of cortical processing or how information flows through the layers of different types of cortex.  The novelty I present here is based on my interpretation of the seminar.)

In the other section of his talk, he showed recordings from layer five thick-tufted pyramidal cells in barrel cortex, and a part of the brainstem called POm.  My understanding of this part was more hazy, but I believe he showed there is a cortico-thalamic-cortico feedback loop that acts as a threshold detector for input.  His goal in identifying this feedback loop was to give insight into rat decision making, but to this graduate student studying barrel cortex in rats seems like an indirect way to study decision making.

Given he was a Nobel winner, I came into the talk with high expectations, which could not be met.  Sakmann spoke to a packed house, as all Nobel winner's do.  The faculty in attendance were extremely deferential, which was highly unusual.   To these expectations Sakmann presented interesting, but not groundbreaking work, and if anyone else were presenting it, the crowd would have been 1/10th the size. His speaking style was assured, but uninspiring.  As I mentioned at the start, Nobel winners have two choices: to present what they're famous for, or present what they care about now.  And given the magnitude of what they're famous for, everything else pales in comparison.  Maybe that is the Nobel winner's curse, to set such high standards that you cannot help but disappoint in the future.

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