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Protein Plays Role in Long-Term Memory



NEW YORK (Reuters Health) - A protein in the brain with suspected links to the circadian clock appears to play a role in long-term memory, according to findings published in the June 23rd issue of Science.

If further study shows that the protein, called NPAS2, is also involved in the body's internal clock, then it could reveal a connection between circadian rhythm and complex brain functions such as learning and memory.

``Behavior of organisms, including learning and memory, is determined by both environmental as well as genetic influences that are largely unknown,'' Dr. Joseph A. Garcia of the University of Texas Southwestern Medical Center in Dallas told Reuters Health. Garcia led the team of researchers that studied the behavior of mice with and without the protein called NPAS2, which regulates specific genes in the brain.

``Mice that lack normal NPAS2 have decreased long-term memory for sights, places, smell, and sound associated with an aversive event,'' explained Garcia. ``These results may have implications in humans for learning and memory as well as for certain psychiatric disorders including autism, depression, and mental retardation.''


  The researchers trained mice with and without the protein by giving them a mild electric shock immediately after they heard a specific sound. When the mice were placed in the same environment 24 hours later to test their memory, those missing NPAS2 showed significantly less ``freezing'' behavior--holding stock still, an indication of fear--than those who had the protein.

There were no differences between the two groups in the test given 30 minutes after training, indicating that short-term memory wasn't affected by the protein.

In another test to see if the mice remembered the sound that cued the electric shock, the researchers put the animals in a new environment, but used the same sound. Before the sound was played, the two groups of mice behaved similarly, but after it, the mice missing NPAS2 again showed less fear behavior, indicating that they didn't remember the sound.

``NPAS2 appears to be required for the processing of complex sensory information,'' the researchers conclude. The protein is found in all vertebrates, they note, and only in cells of the nervous system.

In the report, Garcia's team note that the closest relative of NPAS2 is the CLOCK protein, the ``master regulator of circadian rhythm.'' Previous studies showed that conditioned fear can affect circadian rhythm in lab animals. The findings of this study suggest that NPAS2 may be a link between the learning parts of the brain and those involved in the body clock, which regulates sleep-wake cycles, hormone secretion, and various other body functions that follow daily rhythms.

If further study shows that NPAS2 does play a role in circadian rhythm, the researchers speculate, then it may mean that the rhythmic expression of genes play a role in the brain's ability to perform complex tasks, such as learning and laying down memories. Such a finding may lead to new ways to treat learning disorders and some psychiatric diseases that involve these brain circuits.

SOURCE: Science 2000;288:2226-2230.


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