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

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 ."

Related Stories

Researchers make new finding about how memory is stored

Apr 23, 2008

Researchers at Wake Forest University School of Medicine are the first to show that the location of protein-destroying “machines” in nerve cells in the brain may play an important role in how memories are formed – a ...

Memory's master switch

Jul 29, 2010

Neuroscientists have long wondered how individual connections between brain cells remain diverse and "fit" enough for storing new memories. Reported in the prestigious science journal Neuron, a new study led by Dr. Inna S ...

Scientists capture the first image of memories being made

Jun 18, 2009

The ability to learn and to establish new memories is essential to our daily existence and identity; enabling us to navigate through the world. A new study by researchers at the Montreal Neurological Institute ...

Recommended for you

New test to help brain injury victims recover

1 hour ago

A dynamic new assessment for helping victims of trauma to the brain, including those suffering from progressive conditions such as dementia, has been developed by a clinical neuropsychologist at the University ...

See-through sensors open new window into the brain

3 hours ago

(Medical Xpress)—Developing invisible implantable medical sensor arrays, a team of University of Wisconsin-Madison engineers has overcome a major technological hurdle in researchers' efforts to understand ...

User comments