New Findings from SUNY Downstate Resolve Controversy over PKMzeta in Maintaining Memory
May 17, 2016
Closely Related Molecule Used in the Absence of PKMzeta
Brooklyn, NY – New research led by SUNY Downstate Medical Center shows that mice devoid of PKMzeta, a molecule previously identified by SUNY Downstate scientists as essential to memory formation and storage, recruit a closely related molecule, PKCiota/lambda, to make up for the missing PKMzeta.
“The function of the persistently active PKC isoform, PKMzeta, in maintaining long-term potentiation and long-term memory has been challenged by PKMzeta-null mice that preserve these fundamental processes,” said Todd C. Sacktor, MD, distinguished professor of physiology and pharmacology, anesthesiology, and neurology at SUNY Downstate, “but the most closely related isoform, PKCiota/lambda, becomes persistently active in the mutant mice and compensates for PKMzeta.” Long-term potentiation or LTP is a lasting enhancement of signal transmission between neurons believed to be key to long-term memory.
The research also confirms that PKMzeta is necessary for memories in normal animals, as previous research had indicated. The findings were published online by eLife, in an article titled, “Compensation for PKMzeta in long-term potentiation and spatial long-term memory in mutant mice.”
Following the initial discovery of the role played by PKMzeta in memory, later published research cast doubt on the importance of PKMzeta in memory creation and retention, because mice bred without PKMzeta (called “null” mice) could nonetheless form and retain memories.
The new research led by Dr. Sacktor – a co-investigator of the original PKMzeta study at Downstate – shows that mice are able to use the related molecule (PKCiota/lambda) to mimic the effect of PKMzeta.
Moreover, null mice lose the ability to retain memories when given a substance that cancels the PKCiota/lambda, whereas normal animals do not lose memory function if given the same substance.
“Our latest research verifies that our original studies were correct in asserting that PKMzeta is necessary to create and retain long-term memories,” Dr. Sacktor explained. “At that time, we also demonstrated that canceling PKMzeta also erases memories, but without harming the animal’s ability to form new memories at a later date.”
He continued, “The ability of animals devoid of PKMzeta to recruit a related substance to take the place of PKMzeta shows the durability of the brain’s memory system and may suggest new pathways of treating memory disorders in the future.”
Publication of the article was made possible by grants from the National Institute of Mental Health (NIMH): MERIT Award R37 MH057068, and RO1 MH53576; and from the National Institute on Drug Abuse (NIDA): R01 DA034970. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, NIDA, or the National Institutes of Health (NIH).
The citation for the article is: Tsokas P, Hsieh C, Yao Y, Lesburguères E, Wallace EJC, Tcherepanov A, Jothianandan D, Hartley BR, Pan L, Rivard B, Farese RV, Sajan MP, Bergold PJ, Hernández AI, James Cottrell JE, Shouval HZ, Fenton AA, Sacktor TC. 2016. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice. eLife 5:e14846. doi: 10.7554/eLife.14846.
About SUNY Downstate Medical Center
SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient’s bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, College of Nursing, School of Health Professions, a School of Graduate Studies, School of Public Health, University Hospital of Brooklyn, and a multifaceted biotechnology initiative including the Downstate Biotechnology Incubator and BioBAT for early-stage and more mature companies, respectively.
SUNY Downstate ranks twelfth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school.