Helping your mom make pancakes when you were three… riding a bike without training wheels… your first romantic kiss: How do we retain vivid memories of events long ago? As described in an article published online on April 25 in Neuronresearchers at the Albert Einstein College of Medicine have found the explanation.
“The ability to learn new information and store it for long periods is one of the brain’s most remarkable features,” said Robert H. Singer, Ph.D., co-author of the paper. “We have made an amazing discovery in mice regarding the molecular basis for creating these long-term memories.” Dr. Singer is the Dominick P. Purpura Professor of Cell Biology and Professor of Neuroscience, Chair Emeritus of Anatomy and Structural Biology, and Director of the RNA Biology Program at Einstein.
Some aspects of the cellular basis of memory were already known. They are made by neurons (nerve cells) and are stored in a region of the brain called the hippocampus. They form when repeated neural stimulation strengthens synapses, the connections between nerve cells. Proteins are necessary to stabilize the long-lasting synaptic connections necessary for long-term memories. The blueprints for these proteins are messenger RNA (mRNA) molecules, which, in turn, are transcribed (copied) from memory-associated genes.
“The paradox is that it takes a long time (several hours) to form a lasting memory, but the mRNAs and proteins associated with making proteins are gone in less than an hour,” said Sulagna Das, Ph.D., first and last. Corresponding co-author of the paper and Research Assistant Professor of Cell Biology at Einstein. “How is it possible?”
To answer that question, the research team developed a mouse model in which they fluorescently labeled all mRNA molecules flowing from Bow, a critically important gene for turning our activities and other experiences into long-term memories. The researchers stimulated synapses in neurons in the mouse hippocampus and then, using high-resolution imaging techniques they developed, observed the results in individual nerve cells in real time.
To their astonishment, they observed that a single stimulus in the neuron triggered numerous cycles in which the gene encoding memory Bow produced mRNA molecules that were then translated into Arc proteins that strengthen synapses.
“We saw that some of the protein molecules created from that initial synaptic stimulus go back to Bow and reactivate it, starting another cycle of mRNA formation and protein production, followed by several others,” said Dr. Singer.
“With each cycle, we saw more and more proteins accumulate to form ‘hot spots’ in the synapse, which is where memories are cemented into place. We discovered a previously unknown feedback loop that explained how the mRNAs and proteins of short lives create lasting memories,” said Dr. Das.
Consider what is involved in memorizing a poem, Dr. Singer suggested: “To make a lasting memory requires that you read the poem repeatedly, and each reading can be thought of as an intermittent stimulus that adds memory-building protein to the synapse.”
Dr. Das noted that the defective expression of the Bow The gene has been implicated in memory difficulties in humans and is linked to neurological disorders, including autism spectrum disorder and Alzheimer’s disease. “What we learn about BowThe response to nerve cell stimulation may provide information about the causes of these health problems,” he noted.
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