Featured Research

from universities, journals, and other organizations

In search of the memory molecule, researchers discover key protein complex

Date:
June 26, 2011
Source:
Brandeis University
Summary:
Have a tough time remembering where you put your keys, learning a new language or recalling names at a cocktail party? New research points to a molecule that is central to the process by which memories are stored in the brain.

The CaMKII molecule has 12 lobes (6 are shown here), each of which has enzymatic activity. This molecule can bind to the NMDA receptor, forming a complex. The number of such complexes at the synapse may increase the amount of memory that can be stored.
Credit: Neal Waxham

Have a tough time remembering where you put your keys, learning a new language or recalling names at a cocktail party? New research from the Lisman Laboratory at Brandeis University points to a molecule that is central to the process by which memories are stored in the brain.

Related Articles


A paper published in the June 22 issue of the Journal of Neuroscience describes the new findings.

The brain is composed of neurons that communicate with each other through structures called synapses, the contact point between neurons. Synapses convey electrical signals from the "sender" neuron to the "receiver" neuron. Importantly, a synapse can vary in strength; a strong synapse has a large effect on its target cell, a weak synapse has little effect.

New research by John Lisman, professor of biology and the Zalman Abraham Kekst chair in neuroscience, helps explain how memories are stored at synapses. His work builds on previous studies showing that changes in the strength of these synapses are critical in the process of learning and memory.

"It is now quite clear that memory is encoded not by the change in the number of cells in the brain, but rather by changes in the strength of synapses," Lisman says. "You can actually now see that when learning occurs, some synapses become stronger and others become weaker."

But what is it that controls the strength of a synapse?

Lisman and others have previously shown that a particular molecule called Ca/calmodulin-dependent protein kinase II (CaMKII) is required for synapses to change their strength. Lisman's team is now showing that synaptic strength is controlled by the complex of CaMKII with another molecule called the NMDAR-type glutamate receptor (NMDAR). His lab has discovered that the amount of this molecular complex (called the CaMKII/NMDAR complex) actually determines how strong a synapse is, and, most likely, how well a memory is stored.

"We're claiming that if you looked at a weak synapse you'd find a small number of these complexes, maybe one," says Lisman. "But at a strong synapse you might find many of these complexes."

A key finding in their experiment used a procedure that reduced the amount of this complex. When the complex was reduced, the synapse became weaker. This weakening was persistent, indicating that the memory stored at that synapse was erased.

The experiments were done using small slices of rat hippocampus, the part of the brain crucial for memory storage.

"We can artificially induce learning-like changes in the strength of synapses because we know the firing pattern that occurs during actual learning in an animal," Lisman says.

To prove their hypothesis, he explained, his team first strengthened the synapse, eventually saturating it to the point where no more learning or memory could take place. They then added a chemical called CN-19 to the synapse, which they suspected would dissolve the CaMKII/NMDAR complex. As predicted, it did in fact make the synapse weaker, suggesting the loss of memory.

A final experiment, says Lisman, was the most exciting: They started out by making the synapse so strong that it was "saturated," as indicated by the fact that no further strengthening could be induced. They then "erased" the memory with the chemical CN-19. If the "memory" was really erased, the synapse should no longer be saturated. To test this hypothesis, Lisman's team again stimulated the synapse and found that it could once again "learn." Taken together, these results demonstrated the ability of CN19 to erase the memory of a synapse -- a critical criterion for establishing that the CaMKII/NMDAR complex is the long sought memory storage molecule in the brain.

Lisman's team used CN19 due to previous studies, which indicate that the chemical could affect the CaMKII/NMDAR complex. Lisman's team wanted to show that CN19 would decrease the complex in living cells. Several key control experiments proved this to be the case.

"Most people accept that the change in the synapses that you can see under the microscope is the mechanism that actually occurs during learning," says Lisman. "So this paper will have a lot of impact -- but in science you still have to prove things, so the next step would be to try this in an actual animal and see if we can make it forget something it has previously learned."

Lisman says that if memory is understood at the biochemical level, the impact will be enormous.

"You have to understand how memory works before you can understand the diseases of memory."

Lisman assembled a large team to undertake this complex research. A key collaborator was Magdalena Sanhueza, who once worked with Dr. Lisman at Brandeis, and her student, German Fernandez-Villalobos, both now of the University of Chile, Department of Biology and Ulli Bayer of the University of Colorado Denver School of Medicine, Department of Pharmacology, who developed CN19, a particular form that could actually enter neurons.

Others involved include Nikolai Otmakhov and Peng Zhang from Brandeis and Gyulnara Kasumova, who worked in the Lisman laboratory for several years as an undergraduate. An additional group contributing to the work was that of Johannes Hell, Professor of Pharmacology at the UC Davis School of Medicine. He and his student, Ivar S. Stein, used immunoprecipitation methods to actually show that the CN19 had dissolved the CaMKII/NMDAR complex.


Story Source:

The above story is based on materials provided by Brandeis University. The original article was written by Susan Chaityn Lebovits. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. Sanhueza, G. Fernandez-Villalobos, I. S. Stein, G. Kasumova, P. Zhang, K. U. Bayer, N. Otmakhov, J. W. Hell, J. Lisman. Role of the CaMKII/NMDA Receptor Complex in the Maintenance of Synaptic Strength. Journal of Neuroscience, 2011; 31 (25): 9170 DOI: 10.1523/JNEUROSCI.1250-11.2011

Cite This Page:

Brandeis University. "In search of the memory molecule, researchers discover key protein complex." ScienceDaily. ScienceDaily, 26 June 2011. <www.sciencedaily.com/releases/2011/06/110623130946.htm>.
Brandeis University. (2011, June 26). In search of the memory molecule, researchers discover key protein complex. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2011/06/110623130946.htm
Brandeis University. "In search of the memory molecule, researchers discover key protein complex." ScienceDaily. www.sciencedaily.com/releases/2011/06/110623130946.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Tryptophan Isn't Making You Sleepy On Thanksgiving

Tryptophan Isn't Making You Sleepy On Thanksgiving

Newsy (Nov. 27, 2014) — Tryptophan, a chemical found naturally in turkey meat, gets blamed for sleepiness after Thanksgiving meals. But science points to other culprits. Video provided by Newsy
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) — Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins