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Gene Variation Affects Memory
By Nancy Touchette

Some people are better at remembering things than others. Aunt Ida might recall in vivid detail what she ate at the Bluebird Restaurant during that vacation to Maine in 1978. Cousin Freddie, on the other hand, might not remember what he had for dinner last night.

The difference may be partly due to a common gene variation that can influence our ability to recall past events.

Pictures used during memory test.

Researchers have used state-of-the-art imaging techniques to probe differences in brain activity among individuals with different versions of a gene important in nerve cell formation. They find that variations in a gene called brain-derived neurotrophic factor (BDNF) can determine whether or not a person is good at remembering past events.

“This is a very important study,” says Michael I. Posner of the University of Oregon in Eugene. “It represents a new way of looking at how genes shape the neural networks in the brain. We can see behavioral differences, and we want to know why these occur. This is about to become a very big field.”

The research is part of a larger effort to understand how genes affect the neural circuits in the brain that control complex behaviors. The technique could also lead to new ways to diagnose, treat, and prevent many neurological diseases, such as Alzheimer’s and schizophrenia.

In the new research, reported in the Journal of Neuroscience, Daniel R. Weinberger and his colleagues at the National Institute of Mental Health in Bethesda, Maryland, studied 28 people who carried genes that encoded either the “Val” form or the “Met” form of the BDNF protein.

Subjects were shown pictures of various scenes and were asked to remember them. Later, they were shown a second set of pictures containing both old and new scenes and were asked which scenes they had seen before.

While the subjects were viewing pictures, the researchers monitored their brain activity using a technique called functional magnetic resonance imaging, or fMRI. The technique shows brain activity during two phases of the memory process: the encoding phase, in which a picture is committed to memory, and the retrieval phase, in which mental images are recalled. The region of the brain known as the hippocampus is the most active during these two phases of memory processing.

People with the "Val" form of BDNF show increased brain activity.

The researchers noticed significant differences in brain activity between the two groups during both the encoding and retrieval phases of the task. Those with the “Val” form of the gene were better at remembering pictures than were those with the “Met” form, and they also had greater brain activity during the encoding and retrieval phases of memory.

The researchers then looked at what determined how well the scenes were remembered. They found that 25 percent of normal variation in the ability to remember the scenes was due to the effect of the variation in the BDNF gene during the encoding phase.

BDNF variation affects normal human memory more than any other previously identified factor,” says Weinberger. “This is an extraordinary effect.”

The technique is especially powerful because it gives a direct picture of what is going on in the brain, which in turn affects behavior. It is often difficult to connect gene mutations to behavior because so many other factors can influence the way a person behaves.

“You can’t behave abnormally without your brain processing information abnormally,” says Weinberger. “But you can have abnormal processing without abnormal behavior.”

People with abnormal brain function often develop other ways to compensate for the deficit, so the direct effects of a gene mutation can go unnoticed. By looking directly at brain activity, researchers can detect changes that may otherwise escape detection.

Weinberger has used similar techniques to look at differences in brain activity among people with mutations in the serotonin transporter gene who are at risk for depression and in mutations of the Apo E4 gene, which is associated with Alzheimer’s disease. Such studies may help researchers detect changes in brain function before the clinical symptoms of the disease appear.

Ultimately, researchers hope the new technology will help them tease out how specific genes affect normal brain function and how variations in these genes can lead to abnormal behavior and disease.

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Hariri, A.R., et al. Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. Journal of Neuroscience 23, 7894-7903 (July 30, 2003).
Hariri, A.R., and D.R. Weinberger. Imaging genomics. British Medical Bulletin 65, 259-270 (2003).

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