Tuesday, September 04, 2007

Memory and long-term potentiation

To begin with, we have an in-depth series of four recent articles by Terry McDermott of the Los Angeles Times on Gary Lynch and his work on the neurobiology of memory. In spite of some minor criticisms, it's as heroic a piece of exposition as one will find in the mass media. You can learn a lot about the current "story" of how memory works by reading these articles.

You can learn a lot more, besides – namely, how science really works. This particular story is quite amazing actually. Lynch's career has had more ups and downs than a roller coaster. I wouldn't be surprised to see the story made into a Hollywood drama before too long.

Except for one thing: it's not over yet. The tight connection between long-term potentiation has been for the last 30 years or so just a hypothesis. Only about a year ago was the paper published that seems to be accepted as the long-awaited verification of the hypothesis. And it's merely one of the ironies of this Byzantine story that this confirmatory paper came out of a laboratory at the other end of the country from Lynch's. Unfortunately, McDermott does not even mention this part of the story. To make up for that, you will find at the end of this note some references to work that has appeared in the past year on long-term potentiation. One of them is about Gary Lynch and his associates and the goal they managed to (finally) achieve.

The most exciting thing about it all is that the accomplishment is just the beginning, not the end of the story. What seems to have been achieved is a technique for actually visualizing memory traces. This should make it possible eventually to map out how memories are laid down in the brain, in a manner that could become as routine as the technique of staining cells for microscopy was 100 years ago.

Unfortunately, I can't quickly summarize the story that McDermott tells in his series of articles. Even though it could take you several hours to read through the whole thing, it's worth it. I wouldn't be surprised to see this turned into a book (and then into the movie) – but you'll learn the story much sooner if you just read the articles.

The text following each item is quoted material, except for editorial comments, which are in color.

One man's epic quest for understanding
Lynch is a neuroscientist at UC Irvine, where he has spent 37 years trying to uncover the biochemical mechanisms of memory.

He has, for almost the length of his career, been trying to answer essentially a single pair of questions: What happens in the brain when a human being encounters a new experience so that he or she can recall it at will tonight, tomorrow, in 2025? And what goes wrong when we can't remember?

Trials, and a series of errors, in the brain lab
Yanagihara one day, finally, working with the brains of young rats, got his experiment to work right, and found the result he was expecting to find. "If we get it tomorrow in middle-aged rats, it's great," he said.

"If you see a garbage can flying out of the lab onto the hedge, you'll know we didn't," Kramar said.

The next day, the trash cans remained inside, but only because nobody had the energy to throw them out the window. The experiment had failed again.

Unfortunately, one can't rely on the technical accuracy of everything written in this series. An example in this part is the confusion of nitric oxide with nitrous oxide. The former is the molecule of greater interest in biology, while the latter is "laughing gas". At least the error is acknowledged in a note within the article. But it makes one wonder just how many other details not so readily checked can be relied upon. Like, for instance, the reference to antibodies as just "chemicals" – well, yes, but...

Breakthroughs, and new crises, in the lab
After weeks of repeated failures on almost every other front, Lynch was ecstatic. "You mean this crap actually works?" he said. "You don't expect to see a result this black-and-white. You expect ambiguity. Aging does not occur uniformly even across a single neuron. It's an instant default explanation for memory loss. It's getting to the point where we might have to start believing we were right."

Another bit of sloppy writing in this installment of the series. In one place it says, correctly, that a neuron has just one axon. Then in the same paragraph it talks about the "axons" of one neuron.

Success and rejection
It seemed fitting, somehow. There he sat at the end of the great, long chase, often sick as a dog, the entry locked, the clamorous tribes of the neurosciences a low hum in the distance; no phone, no e-mail, not even a name on the door to betray his presence. The only way you would know he was there at all was the blue Corvette out front. And, of course, the science, which, no matter the circumstance, difficulty or hour, had poured out for 30 years like water from the well. And poured still.

Memory: a glossary of terms
You might want to keep this glossary open in a separate window if you need help with some of the terminology.

Further references

And now we have some pointers to the additional details, as promised early on.

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