Forget Ritalin and Cramming: Molecular Pathways in the Brain May Reveal the Best Learning Strategies

A computer has modeled the most efficient form of learning, that is, if you're a sea slug running from a lobsters. Scientists hope it might eventually work for a human studying for a calculus midterm

High-school and college teachers always entreat their charges to forgo the cramming. Studying bit by bit over the course of a semester is the way to go. A study published online in Nature Neuroscience on December 25 not only appears to demonstrate the biological underpinnings of this pedagogical truism. It actually goes one step further to suggest a means of optimizing training intervals, an insight that could, in theory, translate into strategies for committing to memory the molecular structure of maitotoxin or a Chinese ideogram.

The study is not about to spur a round of venture financing for the next start-up to launch a new generation of brain-training games. At the moment, it is still just a proof of principle in Aplysia californica, the sea slugs that are star animals in the laboratories of neuroscientists. Eric Kandel, the avuncular regular on the Charlie Rose Brain Series, actually rode the back of Aplysia to a Nobel Prize in 2000 for his research on the biochemical processes underlying memory.

In this new study, Kandel's former student, John H. Byrne, who heads the Department of Neurobiology and Anatomy at The University of Texas Medical School at Houston, has brought a new twist to the original learning method developed in Kandel's lab—a technique that consisted of shocking slug tails at regular intervals and then seeing whether the animals overreacted later when receiving another zap, a sign that they remembered their tormentors all too well.

The question that Byrne and team took upon themselves was to determine whether the chemical reactions that underlie this process could be tweaked in a way to enhance the learning process. The standard method of doing this research replaces slugs with a lab dish containing the animals' nerve cells. Five pulses of the neurotransmitter serotonin (the equivalent of shocks) are applied to slug sensory and motor neurons, each pulse separated by a 20-minute interval. Two enzymes in the neurons activate proteins called transcription factors that turn on genes. This initiates production of new proteins that strengthen the firing of neurons, signals that are the equivalent of "I remember this. It hurts."

The two enzymes that initiate this "long-term facilitation" process work in tandem to get things moving. Using the standard timing protocol, the two enzymes do not reach peak activation inside a nerve cell at the same time, a hint that the usual way of doing things might not be the best way.

So Byrne's team deployed a computer to model 10,000 permutations of intervals between pulses to try to coordinate activation of enzymes and to maximize their interaction. The optimal protocol, it turned out, was not the usual, even-spaced one, but an irregular series of two serotonin pulses emitted 10 minutes apart, then one five minutes later, with a final spritz 30 minutes afterward. With this regimen, interaction between the two enzymes rose by 50 percent—an indication that the learning process was operating more efficiently.

So should you be studying Riemann sums every other day for two weeks and then take a month off before going back to them? Too early to say. The timing protocol Byrne found may be the slugs' adaptation to lobster claws crunching their tails. Studying integral calculus might be a bit different. But the implication of Byrne's work is that the best way to learn may not occur in simple time chunks—and that leaves a meaty set of new research questions for neuroscientists to pursue. "The dream of cognitive neuroscience is going from molecules to behavior by way of the brain," says Gary Marcus, a psychologist at New York University, and author of Guitar Zero: The New Musician and the Science of Learning. "This is a terrific step in that direction."

For their part, Byrne and company will now use these same techniques to try to optimize other aspects of the memory formation process in sea slugs. If that proves successful, they may eventually move on to humans. Motor skills would probably be the first target—throwing a baseball, doing the high jump, or helping a stroke victim to walk again. Science homework will have to wait. Researchers know more about the brain circuits in the cerebellum, involved with movement, than in the hippocampus, a locus for initiating the type of factual memories needed for organic chemistry.

Better ways to learn based on brain science would have enormous ramifications for educational practices. "It's not going to be an easy direction to follow because it means a lot of painstaking and detailed work to understand the biochemistry of learning," Byrne says. "But I think what it demonstrates is that if you have that information you may be able to make some big advancements in improving learning abilities by being in sync with the underlying molecular dynamics. Rather than taking cognitive enhancement drugs, you could have better training procedures."

Get out the stopwatch and stash the pill bottle.


Image Source: John Byrne

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