A memorable structure
In the 1950s, when a patient called HM had the hippocampus removed from his brain to control seizures, scientists learned that this small hunk of brain plays a huge role in long-term memory. HM's seizures improved, but he "was no longer able to form or retain long-term memory of facts and events, what we call declarative memory," says New York University neuroscientist Wendy Suzuki.

"He could carry on a conversation and remember what he'd learned in third grade, but if I say 'I'm Wendy, I study memory at NYU,' he would not be able to remember that five minutes later."

The inadvertent experiment "turned the neuroscience community on its ear," says Suzuki. "It was the first strong link between memory function and a particular brain structure."

But decades of experimental advances were needed to understand the behavior of the millions of nerve cells -- neurons -- in the living hippocampus. "Everybody knew the hippocampus was playing some role, but we had very little idea exactly what," Suzuki says. "If you only study a damaged hippocampus, you will never fully understand a normal one."

Monkey see, monkey remember
Today's revolution in brain research, using slick new ways to examine the living brain, is helping unravel the role of the hippocampus. In a study published two months ago, Suzuki and colleagues watched individual neurons change while monkeys learned. The researchers placed an ultra-fine measuring electrode into the hippocampus of rhesus monkeys, and taught them to remember target locations in a complex picture (see "Single Neurons......." in the bibliography). Then the researchers watched the brain change as the monkeys learned to remember where, in each picture, they had to gaze to get some fruit juice.

The recall phase of the experiment began after monkeys learned that they would get a fruit-juice reward by looking at a specific part of a photo:
A: The monkey sees this fascinating scene for 0.3 seconds.
B: This photo appears for 0.5 second
C: A 0.7-second delay shows this scene.
D: Success! If the monkey remembers the correct target (arrow), and looks at it, it gets a slurp of fruit juice. Courtesy: Wendy Suzuki, New York University

In the infinitely complicated electrical network called the brain, individual neurons send electrical signals at characteristic rates, say 10 times a second for neuron A or 50 times a second for neuron B (bet you didn't know each neuron is lettered -- in tiny type...).

To brain researchers, a significant change in firing rate is a response to conditions inside or outside the brain, and a signal to other neurons. Suzuki and Co. saw plenty of responses in their experiment. "Lots of individual cells ... responded to the task, and 28 percent of the responding neurons changed their activity directly in parallel with the learning," she says. "When a monkey was just starting to learn a particular picture, we would see a very striking change in cell activity."

All in the timing
Among the neurons that did change firing in connection with learning, she said, about equal numbers changed before and after the learning. The first group may be helping set up the learning process, while the second may be strengthening the budding memory.

The experimental technique, however, did not allow the researchers to return to individual neurons to see how they had changed over the course of the experiment.

Still, Suzuki says the new work expands on existing studies. "There have been hints of this previously, but this is the most dramatic demonstration." While the learning in one study improved from 50 percent accuracy to only 60 percent, "In ours, they went from 25 percent chance of success [dumb luck] to 100 percent accuracy."

In this MRI, red outlines the right hippocampus in a monkey's brain. The hippocampus (another is on the left side) plays a critical role in memory for names, faces, facts and dates.
Courtesy: Wendy Suzuki, New York University

Brain researchers say that although the hippocampus, in Suzuki's words, "has humongous interconnections with the visual and auditory areas, the frontal lobe, and the neocortex," it does not store declarative memories. Instead, it works like a central switch, directing impulses to the neocortex, the big, folded area on the outside of the brain where memories are warehoused.

And while the hippocampus plays no direct role in emotional memories, it is still crucial to personality. "The kind of memories that the hippocampus and related structures are involved in are particularly interesting to me," says Suzuki, "because memories for the facts and events you have experienced really define you as an individual. Without this, you are essentially no longer you."

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