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Hippocampal Firing Patterns Linked to Memory Recall

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Science  05 Sep 2008:
Vol. 321, Issue 5894, pp. 1280b-1281b
DOI: 10.1126/science.321.5894.1280b

The hippocampus, tucked deep inside the temporal lobes of the brain, has been intensely studied for its role in recording memories. Now two studies—one with rats and one with people undergoing surgery for intractable epilepsy—suggest that patterns of neuron firing in the hippocampus are also involved in recalling past experiences.

Memory aid.

A rat's hippocampus (above) generates sequences of neural firing that may help it remember what to do next.

CREDIT: NEAL MELVIN/2007 OLYMPUS BIOSCAPES COMPETITION (HONORABLE MENTION)

“The two papers are significant because they point directly to reactivation of neural activity sequences as a mechanism for memory recall,” says Edvard Moser, a neuroscientist at the Norwegian University of Science and Technology in Trondheim. Such a mechanism may underlie several functions attributed to the hippocampus, Moser says, including navigation, memory, and planning future actions.

In the rat study, researchers led by Eva Pastalkova and György Buzsáki of Rutgers University in Newark, New Jersey, simultaneously recorded the activity of scores of hippocampal neurons as rodents ran through a maze shaped like a squared-off figure eight. The rats always started the maze by running down the middle of the three arms and then chose to continue down either the left or the right arm. The researchers trained them to alternate between the right and left arms each time they ran the maze. In between runs, the rats spent 10 to 20 seconds on a running wheel.

During this delay period, neurons in the hippocampus fired in sequences that predicted which arm the rat would run next, the researchers report on page 1322. Even in the few cases when a rat goofed and went the wrong way, the preceding firing sequence predicted its mistake. These sequences—which resemble sequences that occur as a rat actually runs through a maze—likely represent the brain's internal mechanism for planning (or reminding itself) what it has to do next, Buzsáki says.

The findings confirm a decade-old prediction that the hippocampus might generate such firing sequences to maintain important information during a delay in a task, says David Redish, a neuroscientist at the University of Minnesota, Minneapolis. Redish notes that consistent patterns of activity emerged only when the rat had something to remember. “When the rat is just running on a wheel for the heck of it in its home cage, they don't see it.”

In the human study, published online this week in Science (www.sciencemag.org/cgi/content/abstract/1164685), researchers led by Hagar Gelbard-Sagiv of the Weizmann Institute of Science in Rehovot, Israel, and Itzhak Fried of the University of California, Los Angeles, recorded from hundreds of neurons in and around the hippocampus of 13 epilepsy patients undergoing operations in which surgeons introduced electrodes into the brain to locate the source of their seizures. The patients watched several 5- to 10-second video clips that depicted a variety of landmarks, people, and animals. A few minutes later, the researchers asked the patients to freely recall the clips they'd just seen and call them out as they came to mind. (Most subjects easily remembered almost all of the clips.) The first time the patients saw the clips, many neurons in the hippocampus and a nearby region, the entorhinal cortex, responded strongly to certain clips and weakly to others—preferring a clip from The Simpsons, say, to ones showing Elvis or Michael Jordan. Later, each neuron began firing strongly a second or two before the subject reported recalling that neuron's preferred clip, but not when the subject recalled another clip.

“Previous work [with animals] has shown that such reactivation occurs during sleep as well as during certain behaviors where memory is needed, but it has remained unclear whether reactivation actually reflects recall of the memory,” say Moser. Fried's findings are exciting because they provide the first direct link between reactivation of hippocampal neurons and conscious recall of a past experience, says neuroscientist Matthew Wilson of the Massachusetts Institute of Technology in Cambridge.

Both studies have implications for an ongoing debate about the relationships among various functions attributed to the hippocampus, says Lynn Nadel, a neuroscientist at the University of Arizona in Tucson. Nadel says that the findings fit with his view that the neural mechanisms underlying spatial navigation, episodic memory, and action planning may be one and the same. “One might say at this point that the available data suggest that the hippocampus is critical for ‘navigating'through space not only in the present but also in the past, to retrieve memories, and in the future, to predict the results of actions,” Nadel says.

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