Brain researchers from UCLA, Johns Hopkins discover role of key protein in converting short-term memories into lifelong ones

May 15, 2001

Scientists from UCLA and Johns Hopkins University have taken the first step in discovering how the brain, at the molecular and cellular level, converts short-term memories into permanent ones. Their study will appear May 17 in the journal Nature.

The study's lead author, postdoctoral researcher Paul Frankland, conducted his work in the laboratory of Dr. Alcino Silva at UCLA's Brain Research Institute. Previous studies, Frankland noted, point to the critical role of the cerebral cortex in establishing lifelong memories. But the neurobiology underlying memory storage has been a mystery.

"Memories last different amounts of time," Frankland said. "You might remember a phone number for just a few minutes, for example, while certain childhood events will be remembered for a lifetime. Our study reveals the role of a protein that must be present in the cortex for information to be converted from short-term into lifelong memories."

In a healthy brain, the hippocampal area stores information on a temporary basis, somewhat like a computer holds data in its random access memory. When the brain converts information into permanent memory, much like writing data to a computer hard drive, the hippocampus interacts with the cerebral cortex. If problems occur in either the hippocampus or cortex, however, memory impairment can result.

To better understand this process, Frankland and his colleagues trained mice to accomplish certain tasks. Half the mice were genetically normal and half had reduced levels of a key protein known as a-CaMKII. The genetically altered mice had normal hippocampal function but impaired cortical function.

Initially, both sets of mice showed an ability to learn, indicating proper functioning of the hippocampus in acquiring short-term memories. When testing took place several days later, the normal mice easily remembered their training. By contrast, the memories of the genetically altered mice were severely impaired, meaning that the protein-deficient cortex did not convert information into permanent form.

"The information simply went away in the genetically altered animals - as if it was never stored in the cortex," Silva said. "This is the first molecular manipulation to affect memory so late after training. It provides new insights into how mice store long-term memories at the molecular and cellular level. Our study indicates that the a-CaMKII protein triggers changes in cell-to-cell communication needed for establishing permanent memories in the cortex. Therefore, these studies provide a key molecular and cellular hint of how we hold on to our oldest memories."

In future studies, the brain researchers plan to study other proteins involved in memory storage. At some point, their discoveries may play a role in developing new treatments for certain types of memory problems in humans.

Working on the study with Frankland and Silva were Masuo Ohno of UCLA and Cara O'Brien and Alfredo Kirkwood of the Department of Neuroscience and the Mind/Brain Institute at Johns Hopkins. Their paper is entitled "a-CaMKII-Dependent Plasticity in the Cortex Is Required for the Establishment of Permanent Memory Traces."

University of California - Los Angeles

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