An enzyme in the brain that behaves like a "continuous motor," constantly strengthening the connections between neurons, appears to be behind long-term memory storage.
The chemical, protein kinase Mζ (PKMζ), is part of a family of over 500 kinase enzymes, most of which transmit outside information into nerve cells.
"Most of these motors are in an inactive state, like an engine in a car that's parked," says Todd Sacktor, a professor of neurology at the State University of New York Downstate Medical Center in New York City. "You have to turn it on by pressing the accelerator; as soon as you take your foot off the accelerator, it stops." But unlike its other family members, PKMζ, which was discovered in 1993, is synthesized when a memory is formed and then "essentially has no controls" and functions continuously, as if it had no "off" switch.
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Sacktor, along with Reut Shema and Yadin Dudai, neurologists at the Weizmann Institute of Science in Rehovot, Israel, set out to determine what would happen if they blocked the enzyme at different intervals after a rat performed a learning task, in this case the recollection of eating an unappetizing meal. Their findings, published in this week's Science: they could erase those memories any time after a rat learned to avoid the unsavory snack by injecting a PKMζ inhibitor called ZIP into a midbrain region, the insular cortex (or insula)—home of the taste-processing gustatory cortex.
There are receptors for neurotransmitters (chemicals that transmit messages between brain cells) in the synapses (spaces) between neurons. PKMζ drives more receptors for the neurotransmitter glutamate, which is linked to learning and memory, to go into the synapse, thus strengthening their connection. "ZIP is a jam that stops the motor from enhancing synaptic strength," Sacktor says, "so, synapses go back to their normal strength and the memory is lost."
The researchers offered the rats water laced with the sugar substitute saccharin. They then gave their subjects an injection that induced nausea—causing the animals to develop a prominent aversion to saccharin-doped water. Afterward, regardless of when ZIP was administered, the rats forgot their saccharin-water intolerance within two hours of receiving the drug. Further, none of the rodents given ZIP (after developing an aversion to the sweetened water) recovered their memory over the course of the 25-day study. The rats could, however, relearn their distaste for the water if put through the drill again.
"I would say it's probably closer to the complete wiping," Sacktor says about the action of ZIP, indicating that it likely destroys all taste memory in the gustatory cortex. "We're erasing the contents of the hard disk … within two hours you could learn that association all over again and keep it."
Sacktor believes that this finding could one day be harnessed to help counteract the effects of post-traumatic stress disorder and to dampen the pain sensation. "Chronic pain is believed to be a strengthening of synapses in the pain pathways, so this could be a treatment for that," he says. "There is no treatment currently."
