Closely related molecule can mimic effect of PKMzeta in mice

May 18 2016

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."

Source: SUNY Downstate Medical Center