PKM-zeta-less adult mice still able to form long-term memories

Published on January 4, 2013 at 3:46 AM · No Comments

A study by Johns Hopkins researchers has shown that a widely accepted model of long-term memory formation - that it hinges on a single enzyme in the brain - is flawed. The new study, published in the Jan. 2 issue of Nature, found that mice lacking the enzyme that purportedly builds memory were in fact still able to form long-term memories as well as normal mice could.

"The prevailing theory is that when you learn something, you strengthen connections between your brain cells called synapses," explains Richard Huganir, Ph.D., a professor and director of the Johns Hopkins University School of Medicine's Department of Neuroscience. "The question is, how exactly does this strengthening happen?"

A research group at SUNY Downstate, led by Todd Sacktor, Ph.D., has suggested that key to the process is an enzyme they discovered, known as PKM-zeta. In 2006, Sacktor's group made waves when it created a molecule that seemed to block the action of PKM-zeta - and only PKM-zeta. When the molecule, dubbed ZIP, was given to mice, it erased existing long-term memories. The molecule caught the attention of reporters and bloggers, who mused on the social and ethical implications of memory erasure.

But for researchers, ZIP was exciting primarily as a means for studying PKM-zeta. "Since 2006, many papers have been published on PKM-zeta and ZIP, but no one knew what PKM-zeta was acting on," says Lenora Volk, Ph.D., a member of Huganir's team. "We thought that learning the enzyme's target could tell us a lot about how memories are stored and maintained."

For the current study, Volk and fellow team member Julia Bachman made mice that lacked working PKM-zeta, so-called genetic "knockouts." The goal was to compare the synapses of the modified mice with those of normal mice, and find clues about how the enzyme works.

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