Protein in brain may be key to storing memory, could help Alzheimer's: study
Thu Apr 19, 3:24 PM
By Sheryl Ubelacker
TORONTO (CP) - Canadian-led scientists have discovered that a certain protein appears to control which brain cells get chosen to store new memories, and they believe the knowledge could one day help people with Alzheimer's disease or other types of brain injury.
In experiments in laboratory mice, an international research team headed by Sheena Josselyn of Toronto's Hospital for Sick Children found that a protein called CREB plays a key role in which neurons become the brain's filing cabinets for memories.
The scientists began by altering a virus, replacing its DNA so it produced large amounts of CREB. The virus was then injected into neurons in the animals' brains, in a region called the amygdala (pronounced a-MIG-da-la) that is associated with memory.
The mice were then put through a series of learning tests, including one in which they were given a mild foot shock when a tone was sounded. In subsequent experiments, when the animals heard the tone - without getting shocked - they froze with fear because they recalled the unpleasant sensation.
"We got a really lovely behavioural enhancement," said Josselyn, a Sick Kids scientist and a professor of physiology at the University of Toronto.
But the researchers were puzzled by the size of the memory response because only about 20 per cent of cells in the amygdala had been injected with the CREB-producing virus.
"So we thought that maybe the ones overexpressing CREB are chosen for memory and that's why we we're seeing such a robust effect," Josselyn said.
To test the theory, the team injected the virus into the brains of mice genetically altered to have decreased CREB production and poor learning abilities.
"So if we just infected about 20 per cent of the neurons in this brain region, we were able to overcome this fairly large learning deficit in these mice," she said.
"It totally rescued them. They looked just like the normal mice."
The researchers, whose work is published in Friday's issue of the journal Science, believe it's the first time anyone's shown how memory is allocated in the adult brain.
The findings suggest they may have tapped into a process that occurs naturally in the brain, said Josselyn. "Maybe neurons are competing against one another to become part of this memory trace that encodes that fear memory."
A sort of "PET scan" for mice that looks at brain activity showed that the CREB-loaded neurons lit up after the animals were exposed to new learning experiences.
"We discovered that the amount of CREB influences whether or not the brain stores a memory," said Alcino Silva, a professor of neurobiology and psychiatry at the University of California-Los Angeles and senior collaborator on the study.
"If a cell is low in CREB, it is less likely to keep a memory. If the cell is high in CREB, it is more likely to store the memory."
Silva said the research could have profound implications for human diseases like Alzheimer's.
"What the study suggests is that CREB is like a tag that identifies certain cells as repositories for memory," Silva said from Los Angeles.
"And it's important that the brain separates memory. The brain is constantly funnelling memory to different sites, and what this study suggests is that CREB is one of those traffic controllers that says, 'Don't store here, why don't you store it there,' so we don't confuse what you've just stored with what you are storing now."
Silva said the hope is that CREB could be injected into a human brain damaged by Alzheimer's or other neurodegenerative diseases or by head trauma to redirect memory storage to healthy neurons.
In Alzheimer's disease, for instance, people not only lose long-established memory, but also grow increasingly unable to store new memories as brain cells die.
"The whole process of memory storage decays quickly," he said. "So it is our hope that if we can develop strategies to direct memory to healthy cells, we may one day postpone the traumatic effects of Alzheimer's disease until we can cure it."
Both Silva and Josselyn believe the concept is possible, although it likely would be at least a decade before such injections would be tested in humans.
"This is very much science fiction-like, it's very much in the future," said Silva. "But you know today's science fiction is tomorrow's medicine." _________________ kyranŠ
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