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“Working memory” decline in normal aging linked to loss of specific receptor

University of Florida researchers have identified a subtype of a specific receptor in the brain that is critical for “working memory,” or the ability to hold information in mind for a short time — an ability that often diminishes with normal aging. In a new study published this week in The Journal of Neuroscience, the UF team details how the loss of that specific receptor predicts the severity of working-memory impairment due to aging.

The researchers further found they could use a drug to positively affect those receptors to enhance working memory in aged rats with cognitive decline. The findings suggest a potential future pathway for drug treatment to target those receptors and improve working memory in humans.

“Working memory is the ability to hold information in mind for a relatively short duration, for example, the ability to look up a phone number and remember it until you get to the phone,” said principal investigator Jennifer L. Bizon, Ph.D., a professor of neuroscience and psychiatry in the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. “The ability to do that simple process of holding information over a period of about 30 seconds is critical for planning and carrying out daily activities and is the foundation for more complex cognitive operations such as decision-making.

“We know across species — rats, non-human primates and people — that working memory declines over the course of the lifespan,” Bizon said. “It’s also very vulnerable in a number of neuropsychiatric diseases, such as schizophrenia.”

Previous studies have pointed to receptors for the neurotransmitter glutamate in working memory function. The new UF study, led by postdoctoral fellow Joseph A. McQuail, is significant because it identifies glutamate receptors containing a specific protein subunit as critical for working memory and its decline across the lifespan.

“Many treatments have sought to broadly modulate these receptors to improve working memory in schizophrenia and other neuropsychiatric diseases and have not been successful,” Bizon said.

The new findings “give us a more selective target for treating working memory deficits,” she said.

The UF research was funded by the National Institutes of Health, the National Science Foundation and the McKnight Brain Research Foundation.

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Michelle Jaffee
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