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Researchers discover recent and remote long-term memories can be uncoupled

A research team at the University of South Carolina School of Medicine Columbia has discovered that deleting an enzyme that is required for the formation of recent long-term memories does not prevent the creation of remote long-term memories.

Typically, an experience is held as a short-term memory for seconds to minutes, and then begins transitioning into recent long-term memory, and eventually, to remote long-term memory. Previously, it was believed that an individual must have recent long-term memory in order to have remote long-term memory, but research from the lab of Michy Kelly, Ph.D., indicates the two can be uncoupled.  

The findings, which were recently published in Current Biology, challenge current theories of learning and memory and have wide-reaching therapeutic implications for age-related cognitive decline and memory loss related to neuropsychiatric conditions.

Kelly, an associate professor in the Department of Pharmacology, Physiology and Neuroscience, was the first to discover PDE11A4 (Phosphodiesterase 11A4) is produced in the hippocampal region of the brain. Her team originally discovered that deletion of PDE11 results in a complete loss of recent long-term memory for social experiences. However, additional research proved remote long-term memory for those same social experiences is preserved or even strengthened.

“Current theory suggests you must have recent long-term memory in order to have remote long-term memory, but our research says 24 hours after an experience you can have zero memory of that experience, then seven days later, you’ll be able to remember it,” Kelly says. “This finding is important to the field because it suggests recent and remote long-term memory can be uncoupled from each other.”

PDE11A4 increases with age, so the team hypothesizes that blunting PDE11A4 production could protect remote long-term memory from age-related cognitive decline. These findings lay the groundwork to develop treatments not only for memory loss related to aging, but also transient global amnesia, epilepsy and traumatic brain injury.

“Right now, there are no drugs that can help retain or retrieve memories that are lost due to aging or neurological diseases, such as Alzheimer’s Disease,” Kelly says. “Our research suggests PDE11 inhibitors may be an option for protecting long-term memory in certain populations.”

Kelly’s team plans to look at how PDE11A4 may interact with the role stress plays in the process of memory creation and retrieval to see if the loss of recent long-term memories caused by PDE11A4 deletion could be mitigated.

The research was published online by Current Biology on July 11 in a paper titled “Loss of Function of Phosphodiesterase 11A4 Shows that Recent and Remote Long-Term Memories Can be Uncoupled.”

Katy Pilarzyk, a doctoral candidate at the School of Medicine Columbia, is lead author on the paper. She is joined by Jennifer Klett, UofSC medical student; Edsel Pena, professor of statistics at UofSC; Latarsha Porcher, research specialist; Abigail Smith, research specialist; and Kelly.

Kelly’s lab is funded by grants from the National Institutes of Health. Her current NIH awards are 1R01AG061200 and 1R01MH101130.

The lab’s research also was supported by a Research Starter Grant in Pharmacology & Toxicology from the PhRMA Foundation, an ASPIRE award from the Office of the Vice President for Research from the University of South Carolina, a Research Development Fund Award from the University of South Carolina School of Medicine, 1R01MH101130 from NIMH, 1R01AG061200 from NIA, and a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation, as well as a Magellan Scholar Award and SURF fellowship from the Office of the Vice President for Research and the Honors College of the University of South Carolina.


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