By David N. Leff

Asked by her teacher to define the word memory, the third-grader responded: ¿My memory is what I forget with.¿

Seeking to define memory in terms of human brain function, neuroscientists turn to the laboratory rat (genus Rattus). This popular research rodent isn¿t all that brainy. It lacks the bulk of the brain¿s cerebral cortex, which marks Homo sapiens and other primates as smarter than most, if not all, mammals.

But what rats have going for them is a brain structure called the hippocampus. This crucial component of memory processing got its name in antiquity for its fancied resemblance to a seahorse. Neuroscientist Howard Eichenbaum, a professor of psychology at Boston University, has a homelier descriptor for the human hippocampus.

¿It¿s like a banana in shape,¿ he told BioWorld Today, ¿and lies along in the temporal lobe of the cerebral cortex. Just imagine a banana 10 centimeters long, pointing right out the tips of your jowls, and backwards to the back of your brain. In rats, which don¿t have much of a cortex, it¿s even relatively larger ¿ a C-shape about two centimeters in length.¿

Rodent and human hippocampi share center stage in a controversy that divides the neuroscience research community.

¿The controversy,¿ Eichenbaum said, ¿is whether in animals the hippocampus is specialized in some ways ¿ dedicated to memory for space, locations, environment ¿ whereas in humans it seems to play a general purpose in organizing memory.¿

In this divergence of opinion, Eichenbaum is on the side of the rats.

¿In the past,¿ he recalled, ¿part of the story that the hippocampus is specialized for space in rats comes from a finding that¿s called place cells.¿ It holds that these hippocampal neurons in the rat become active only when the animal is in a particular location in his environment. And that was a major contributor to this idea that their hippocampus is for remembering spatial environments.¿

Eichenbaum is senior author of an article in today¿s Nature, dated Feb. 18, 1999, titled ¿The global record of memory in hippocampal neuronal activity.¿ (See also BioWorld Today, Jan. 23, 1996, p. 1.)

¿What we were able to show here,¿ he said, ¿using a novel version of a memory test we gave the animal, is that the kind of memory game rats play, they play all over, at many locations in space.¿

The space on which Eichenbaum¿s game took place consisted of a square, black, Plexiglas playing field, or tabletop, one meter per side. The pucks were round, clear plastic cups 12 centimeters (4.5 inches) in diameter and 4.5 centimeters (1.75 inches) deep. The game itself consisted of three innings: a pre-training warm-up; a training session; and electrical recording of neuronal activity in the hippocampi of live rodent team players. Their motivation was to find and eat a tasty trophy of Froot Loop tidbits, hidden at the bottom of selected cups, covered by fine playground sand mixed with one of nine odoriferous spices. These tempting olfactory teasers included cocoa, turmeric, coffee, salt, onion, English breakfast tea, cinnamon, and cumin.

Memories Of Smells And A Froot-Loop Fix

¿In the pre-training stage,¿ Eichenbaum recounted, ¿we put cups of sand containing lots of Froot Loops right in an animal¿s home cage. He¿d initially explore them carefully, find the Froot Loops and eat them. Then he¿s hooked, self-trained, addicted to find all the Froot Loops they can in the scented sand. This fits right into the rodent¿s natural, foraging type of life.

¿Then,¿ he went on, ¿we bring the animals down to the lab and place them on this big tabletop. We can put the cup of scented sand down any old place on that surface, and after a day or so, whenever we position a cup on the tabletop they¿ll run up, dig, and get a Froot Loop. On each trial, we take a cup containing one of the nine possible odors. First trial, we plunk it down at a randomly chosen location. The rat runs over as usual, and digs for the reward. Then, we take the cup away and the animal typically runs into some preferred corner of the apparatus.

¿The next odor is going to be either a match with the previous one or a non-match ¿ one of the other eight odors,¿ Eichenbaum said. ¿If it¿s a match, no Froot Loop. If a non-match, different from the previous one, the rat will find its reward. Then the next trial after that might perhaps be a matching one, no Froot Loop. First time around he digs, doesn¿t find one and gives up. After about 100 trials of this, which takes two to three days, 40 or 50 trials a day, the animals come to the point where they walk over, take a sniff at the cup, and immediately put their paw in to start digging, or they turn their nose way and walk back to their corner to wait for the next trial.

¿They¿ve come to realize,¿ Eichenbaum pointed out, ¿that, if it¿s a match, it doesn¿t pay off, and they don¿t bother to dig. Essentially, the measure of memory is whether or not the animal is going to dig or turn away. Then we can score his correct or incorrect responses. Correct is to dig when it¿s a non-match, and turn away when it¿s a match. They get very good at it; they run over 90 percent correct.¿

Then it¿s time for the neuronal recording session, monitored by fine, 12-micron electrodes implanted painlessly in the brains of the rats. They¿re at the top of their memorized training. ¿At the very last second,¿ Eichenbaum said, ¿just before he sticks his paw in, when he¿s sniffing the odor and generating which response he¿s going to make, is precisely when we start recording those brain waves. When a wire gets very close to a cell body, its tip touches the neuron and picks up the electrical activity, the action potentials of the cell. Typically, we can hold a specific cell all days or a few days. Physiologically, each neuron has a unique character, like interviewing different people. Then, finally, using statistical analysis, we can ask which aspect of the task is controlling the cell¿s activity.¿

¿In a global sort of way,¿ he observed, ¿this finding puts rats and people in the same ballpark. It says rats are a good model for studying memory in people.

¿And that actually sits very well with ideas of memory,¿ Eichenbaum concluded. ¿Neurons change due to repetitive activity, suggesting that these cells are sensitive to this kind of long-term potentiation, which enables neurochemistry and neuropharmacology to create drugs that may be keys to improving memory, or ameliorating deficits of aging and other disorders.¿ n