In search of the memory molecule, a key protein complex discovered

June 23, 2011 in Neuroscience

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. 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 , the contact point between . Synapses convey from the "sender" neuron to the "receiver" neuron. Importantly, a synapse can vary in strength; a strong synapse has a large effect on its , 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 .

"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 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 ."

Provided by Brandeis University search and more info website

5 /5 (8 votes)  

Rank 5 /5 (8 votes)
Related Stories
Relevant PhysicsForums posts

More news stories

For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests

Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...

Neuroscience created May 18, 2013 | popularity 5 / 5 (1) | comments 0 | with audio podcast

Temporal processing in the olfactory system

The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...

Neuroscience created May 17, 2013 | popularity 4 / 5 (1) | comments 0 | with audio podcast report

Melon focus headband turns to Kickstarter for rollout plans

(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...

Neuroscience created May 17, 2013 | popularity 3.7 / 5 (3) | comments 0 | with audio podcast weblog

Deep brain stimulation: A fix when the drugs don't work

Neurological disorders can have a devastating impact on the lives of sufferers and their families.

Neuroscience created May 17, 2013 | popularity 5 / 5 (1) | comments 0 | with audio podcast

Brain makes call on which ear is used for cell phone

If you're a left-brain thinker, chances are you use your right hand to hold your cell phone up to your right ear, according to a newly published study from Henry Ford Hospital in Detroit.

Neuroscience created May 16, 2013 | popularity 2 / 5 (2) | comments 0 | with audio podcast


Researchers identify a potential new risk for sleep apnea: Asthma

Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...

Study finds that sleep apnea and Alzheimer's are linked

A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.

'Gap' for HIV vaccine efforts after latest setback

The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.

Computational tool translates complex data into simplified 2-dimensional images

In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...

New theory on genesis of osteoarthritis comes with successful therapy in mice

Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...

Ginger compounds may be effective in treating asthma symptoms

Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...