New Protein Improves Memory, Offers Insight Into Learning Process

New protein improves memory and helps explain how the brain learns

Posted Mar 12, 2012

"Hi, my name is John."

"Nice to meet you...what was it again?"

Ok, that might be an extreme example of forgetting, but it's not far from the truth; I've forgotten someone's name in a matter of seconds after they told me. 

A recent study in PLoS Biology should give hope to the forgetful. A collaborative research group in Europe, spanning Spain, Switzerland and Denmark, developed a small protein called FGL that enhances memory formation and learning in rats, and now they have some explanation as to why. The study's authors, led by Shira Knafo, César Venero and José Esteban, attribute the improvement from FGL to better connections—and ability to strengthen those connections—between neurons.  This knowledge may eventually improve treatment of some disorders, as the authors explain that these "mechanisms are thought to be responsible for multiple cognitive deficits, such as autism and Alzheimer's disease"

Testing Memory

To see if FGL (short for F G loop peptide) would affect memory, Venero, psychobiologist Karine Cambon and colleagues injected FGL into the brain of 12 rats, and an inactive protein into another 13 rats in a 2004 Journal of Neuroscience study. They then trained all the rats on the Morris water maze task, developed in 1981 by neuroscientist Richard Morris. In the task, a rat is placed in a round pool of murky water with smooth walls so the rat can't escape. A platform, hidden just beneath the surface of the water, is not visible to the rat. The rat learns to navigate to the platform using clues in the room, such as shapes on the wall, so they can stop swimming-a stressful, tiring task-as soon as possible. To test memory, researchers place the rat in the pool and measure the time it takes the rat to find the platform across several days.  A decrease in swim time means that the rat learned to use these clues to find the platform and found the platform faster than on previous days.

The rats who were injected with FGL found the platform more quickly than the rats injected with the inactive protein. FGL improved their ability to learn the layout of the room. In the words of the authors, "This work demonstrates that cognitive function can be improved pharmacologically."  Yet at the time, despite the memory improvement they found, the authors could only speculate how it worked.  In this new study, they offer evidence that might explain the memory boost.  

How it might work

In their most recent article, the authors suggest that FGL improves the brain's ability to modify the connections between neurons, the cells that are the building blocks of the brain.  When examining neurons that had been treated with FGL, Knafo, Venero and Esteban found that they had higher levels of a receptor, AMPA, critical for modifying neuronal connections.

As the authors write, "The human brain contains trillions of neuronal connections, called synapses, whose pattern of activity controls all our cognitive functions. These synaptic connections are dynamic and constantly changing in their strength and properties, and this process of synaptic plasticity is essential for learning and memory. In this study, we show that synapses can be made more plastic using a small protein."  

Many neuroscientists consider understanding plasticity the Holy Grail for learning and memory; once we understand plasticity, we will understand how the brain learns.

Can We Use It to Study for a Test? 

FGL hasn't been tested in humans yet. The basic architecture of the human brain is the same as the rats, but there are some differences. Furthermore, even in the rats they had to inject FGL directly into the brain, something distant on the horizon for most humans. Until these results can be replicated in humans, any conclusions are speculative.

Although it offers promise, it also begs caution, at least for the healthy. As exciting as improving memory might be, using this technique may have unintended consequences. Our brains already have built-in mechanisms that sear important details into memory, such as the ability to remember where you were when you heard about 9/11. The amazing feature of our natural memory ability is its specificity. While you remember 9/11, you may or may not remember where you were when you got the spatula in your kitchen, but does it really matter? It's unlikely to come up in conversation, and if it did, your most important concern, rather than remembering how you got it, may be changing the subject to a more interesting topic.

FGL may improve memory, but possibly without discrimination, leaving you with more banalities. Or, possibly, FGL could turn your brain into a super-computer, and you could remember all the things you want.  You could retake all those tests you failed and get the grades your parents wanted to brag about, or at least you wouldn't feel so foolish having to ask someone's name for the second or third time (why are names so hard to remember?). To me, that's the neat thing about it: it's possible.   

photo credit: brittanyhock


Knafo S, Venero C, Sánchez-Puelles C, Pereda-Peréz I, Franco A, Sandi C, Suárez LM, Solís JM, Alonso-Nanclares L, Martín ED, Merino-Serrais P, Borcel E, Li S, Chen Y, Gonzalez-Soriano J, Berezin V, Bock E, Defelipe J, Esteban JA. Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement. PLoS Biol. 2012 Feb;10(2):e1001262. Epub 2012 Feb 21. PubMed PMID: 22363206; PubMed Central PMCID: PMC3283560.

Cambon K, Hansen SM, Venero C, Herrero AI, Skibo G, Berezin V, Bock E, Sandi C. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci. 2004 Apr 28;24(17):4197-204. PubMed PMID: 15115815.

Thanks to Anne Hart for sharing her expertise on the brain's role in learning and memory.