CREB And Memory
In the complex process of memory formation new research is making one family of molecules stand out in the pack of players. Many believe cyclic amp-response element binding protein and its cousins are essential for the process of sealing memories in the mind. They hope that zeroing in on the molecules will lead to therapies that manipulate memory. New drugs would boost memory or possibly dissolve traumatic recollections.
A drug that velcros the elements of the periodic table in your mind for the big exam. A fountain of youth cocktail that counters the decline in memory seen in many people over age 50. Or a therapy that erases the persistent recollections of a childhood trauma. Antidotes dreamed up in a sci-fi flick? Maybe. A more interesting notion is that forms of these compounds may become a reality over the next decade or so. Currently researchers are focusing most of their hope on the development of a treatment for severe memory deficits.
The optimism stems from mounting evidence that shows the molecule cyclic AMP-response element binding protein (CREB) is one of the cornerstones of enduring memories. While many memories last the equivalent of a finger snap, some are promoted to long-term status. Perks include a pass into our mental library that remains valid for days, weeks or longer. Long-term memories help us recognize a familiar face in a crowd or remind us how to hit a serve during a tennis match.
Scientists recent discoveries that CREB is involved in the memory process are leading to:
* New memory-targeting treatments that scientists believe will be tested in humans within 10 to 15 years.
* A greater understanding of how CREB and related gene-regulating proteins interact to build lasting memories.
Studies of the sea slug offered the first hints that CREB had a stake in memory. In 1990 researchers snipped out a set of the slug's nerve cells, or neurons, that are involved in memory storage. They found that adding a CREB-disrupting compound halts the molecular long-term memory process. This sign of CREB's involvement in memory launched a series of studies that deciphered the process in sea slugs, and in organisms that are capable of forming more complex types of long-term memories.
Research revealed that CREB has two family members -- the CREB activator and the CREB repressor proteins. The activator's agenda is to promote long-term memory formation. The repressor fights to forget the memory.
In one study, scientists found that they could either speed up the formation of memories or block them by altering the levels of repressor and activator. Normally, following 10 training sessions with a short rest in-between each one, fruit flies retain the information that an odor signals that a shock is coming. Flies with extra activator had a souped-up memory ability. They could secure a lasting memory after only one lesson. Flies that over-produced the repressor, however, could not form a specific long-term memory, even after many training sessions.
Researchers found that alterations of activator and repressor levels also affected the memories in rodents when they had to complete more complex tasks. For example, in one test mice had to rely on lasting memories to locate a hidden dock in a pool of water. In another, they had to choose a meal that matched the smell of a fellow mouse's breath. Researchers found that mice bred to produce low levels of CREB activator could not properly create the long-term memories needed to carry out tested assignments. Some researchers believe, however, that the deficit may not have simply resulted from the defective molecule. Developmental problems also may have arisen due to the technique used to cripple CREB.
But another study used a different method to impair CREB in rats and found similar results. The researchers also pinpointed the hippocampus as one of the brain areas where CREB exerts its power. Mature rats had their CREB activity disrupted, solely in the hippocampus. In turn they showed a deficiency in long-term memory function.
Currently, scientists are testing a large number of existing drugs that may be able to enhance memory by affecting CREB in rodents.
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Scientists believe that the process of creating lasting memories begins when the neuron's endings, or dendrites, receive signals (1). The signals induce reactions involving protein kinase A, which in turn set off CREB activator in the nucleus (2). The jump-started CREB protein activates genes in the cell's DNA. The genes are transcribed into messenger RNA (3) which is used as a blueprint to produce proteins that secure a memory (4).
For more information please contact Leah Ariniello, Science Writer, Society for Neuroscience, 11 Dupont Circle, NW, Suite 500, Washington DC 20036.