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Long-term memory has back-up plan, researchers find

Date:
May 17, 2016
Source:
New York University
Summary:
A team of scientists has identified the existence of a back-up plan for memory storage, which comes into play when the molecular mechanism of primary long-term memory storage fails.
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A team of scientists has identified the existence of a back-up plan for memory storage, which comes into play when the molecular mechanism of primary long-term memory storage fails.

Previous work had shown that mice engineered without an enzyme crucial to long-term memory storage could still form such memories, creating a controversy that a team of scientists has now resolved with the new research, which appears in the journal eLife.

The research focused on an enzyme made in nerve cells -- PKMζ (PKMzeta). In a series of experiments, they confirmed that while the enzyme is crucial to long-term memory in normal mice, the mice engineered without PKMζ still form long-term memories because they deploy an alternative, previously silent memory-storage method.

"Mice missing the PKMζ enzyme essential for long-term memory are able to recruit a back-up mechanism for long-term memory storage," explains André Fenton, a professor in NYU's Center for Neural Science and one of the paper's co-authors. "The question now is: how does PKMζ function and what is the mechanism of its interaction with the PKCλ/ι backup mechanisms?"

Previous research has found PKMζ plays an important role in long-term memory storage, which scientists believe depends on the persistent strengthening of the connections between nerve cells. Specifically, the enzyme is made during the strengthening of these connections, and it remains in place so long as the links remain strong.

Notably, studies examining the role of PKMζ's in memory found that when the enzyme's function was weakened in rodents,after they formed long-term memory, the animals could no longer remember diverse types of memories depending on diverse parts of the brain, suggesting that PKMζ is a general memory storage mechanism.

But, recently, the importance of PKMζ was questioned by experiments on genetically engineered "knockout" mice in which the gene that makes PKMζ was deleted. Without PKMζ, the knockout mice could still strengthen connections between nerve cells and still learn and remember.

While some took these results as evidence that PKMζ's role had previously been overstated, such studies did not consider the possibility of a "back-up" mechanism for memory that takes over when PKMζ is removed. So the question remained: Is PKMζ unimportant for memory or, in its absence, is a back-up mechanism deployed?

To address this matter, Panayiotis Tsokas, a research professor in Todd Sacktor's lab at SUNY Downstate Medical Center, Fenton, and their colleagues tested both the "PKMζ is unimportant" and "PKMζ is compensated" hypotheses. To do so, they used a piece of modified DNA as a drug to block the formation of PKMζ. If another molecule or molecules act as a back-up mechanism for PKMζ, the scientists reasoned, the new drug would block the formation of memory in normal mice, but would have no effect on memory in the knockout mice that cannot make PKMζ -- the drug would have nothing to work on.

The results supported the PKMζ is compensated hypothesis -- the formation of memories normal mice was disrupted while that for the knockout mice was not, confirming the importance of PKMζ, but also pointing to the presence of a back-up mechanism, which they identified involves PKCλ/ι, the most closely related molecule to PKMζ.


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Materials provided by New York University. Note: Content may be edited for style and length.


Journal Reference:

  1. Panayiotis Tsokas, Changchi Hsieh, Yudong Yao, Edith Lesburguères, Emma Jane Claire Wallace, Andrew Tcherepanov, Desingarao Jothianandan, Benjamin Rush Hartley, Ling Pan, Bruno Rivard, Robert V Farese, Mini P Sajan, Peter John Bergold, Alejandro Iván Hernández, James E Cottrell, Harel Z Shouval, André Antonio Fenton, Todd Charlton Sacktor. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice. eLife, 2016; 5 DOI: 10.7554/eLife.14846

Cite This Page:

New York University. "Long-term memory has back-up plan, researchers find." ScienceDaily. ScienceDaily, 17 May 2016. <www.sciencedaily.com/releases/2016/05/160517083205.htm>.
New York University. (2016, May 17). Long-term memory has back-up plan, researchers find. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2016/05/160517083205.htm
New York University. "Long-term memory has back-up plan, researchers find." ScienceDaily. www.sciencedaily.com/releases/2016/05/160517083205.htm (accessed May 25, 2017).

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