Neurobiologists gain new insights into brain and memory

Oct 19 2005

We often make unwise choices although we should know better. Thunderstorm clouds ominously darken the horizon. We nonetheless go out without an umbrella because we are distracted and forget. But do we? Neurobiologists at the Salk Institute for Biological Studies carried out experiments that prove for the first time that the brain remembers, even if we don't and the umbrella stays behind. They report their findings in the Oct. 20th issue of Neuron.

"For the first time, we can a look at the brain activity of a rhesus monkey and infer what the animal knows," says lead investigator Thomas D. Albright, director of the Vision Center Laboratory.

First author Adam Messinger, a former graduate student in Albright's lab and now a post-doctoral researcher at the National Institute of Mental Health in Bethesda, Md. compares it to subliminal knowledge. It is there, even if doesn't enter our consciousness.

"You know you've met the wife of your work colleague but you can't recall her face," he gives as an example.

Human memory relies mostly on association; when we try to retrieve information, one thing reminds us of another, which reminds us of yet another, and so on. Naturally, neurobiologists are putting a lot of effort into trying to understand how associative memory works.

One way to study associative memory is to train rhesus monkeys to remember arbitrary pairs of symbols. After being shown the first symbol (i.e. dark clouds) they are presented with two symbols, from which they have to pick the one that has been associated with the initial cue (i.e. umbrella). The reward is a sip of their favorite fruit juice.

"We want the monkeys to behave perfectly on these tests, but one of them made a lot of errors," recalls Albright. "We wondered what happened in the brain when the monkeys made the wrong choice, although they had apparently learned the right pairing of the symbols."

So, while the monkeys tried to remember the associations and made their error-prone choices, the scientists observed signals from the nerve cells in a special area of the brain called the "inferior temporal cortex" (ITC). This area is known to be critical for visual pattern recognition and for storage of this type of memory.

When Albright and his team analyzed the activity patterns of brain cells in the ITC, they could trace about a quarter of the activity to the monkey's behavioral choice. But more than 50 percent of active nerve cells belonged to a novel class of nerve cells or neurons, which the researchers believe represents the memory of the correct pairing of cue and associated symbol. Surprisingly, these brain cells kept firing even when the monkeys picked the wrong symbol.

"In this sense, the cells 'knew' more than the monkeys let on in their behavior," says Albright.

And although behavioral performance is generally accepted to reliably reflect knowledge, in fact, behavior is heavily influenced – in the laboratory and in the real world – by other factors, such as motivation, attention and environmental distractions.

"Thus behavior may vary, but knowledge endures," concluded Albright, Messinger and their co-authors in their Neuron paper. The other co-authors are Larry R. Squire, a professor in the Department of Psychiatry at the UCSD School of Medicine, and Stuart M. Zola, director of the Yerkes National Primate Research Center in Atlanta.

http://www.salk.edu/