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Photo: Alex Dranovsky, M.D.,Ph.D. assistant professor of clinical psychiatry
New neurons created during adulthood appear to improve some types of memory but impair other types.
New neurons created during adulthood appear to improve some types of memory but impair other types. In the photo, neurons created during adulthood in the mouse hippocampus appear in white.
Every day, your brain creates thousands of new neurons. If your first reaction is “thank goodness,” read on.
   Though one new study by CUMC researchers shows that new neurons enhance long-term memory, a second study by the same lab shows that the neurons also impair a form of short-term memory. The two contrasting results illustrate a theme that is starting to emerge in the still nascent study of neurogenesis – new neurons do not always improve the brain’s performance and they may sometimes be detrimental.
   “We will have to be careful in the future if we prescribe drugs that are meant to increase neurogenesis,” says Rene Hen, Ph.D., professor of pharmacology and the senior author of both papers. “Drugs that improve one type of memory may cause deficits in others.”
   Until a decade ago, the idea that new neurons could sprout in the brains of adult primates was generally dismissed. Evidence had been building for years that the brains of lower primates, rodents and even birds create new neurons during adulthood. The old dogma that humans could not make new neurons in adulthood was finally overthrown in the late 1990s, when new techniques were developed that unequivocally spotted new neurons in the human hippocampus.
   Now the question for neuroscience is not whether these neurons exist, but what are they doing? Because the hippocampus is a focal point for the formation and retrieval of memories, many researchers believe that the new neurons may be essential for learning and memory.
   The first paper from Dr. Hen’s lab, published last November in the Proceedings of the National Academy of Sciences, backs up this theory. Dr. Hen and his graduate student Michael Saxe, Ph.D., showed that a specific type of long-term memory is impaired when the hippocampus can no longer create new neurons.
   In the study, Dr. Saxe set the mice in a container, where they received mild electric shocks. A day later, he returned the mice to the same container. Normal mice froze, indicating they remembered the shocks. Mice that could not make any new neurons moved around the chamber more actively, seemingly with less memory of the day before.
   “The results suggest that new neurons are making an essential contribution to certain types of memory,” says Dr. Saxe, who is now a postdoc at the Salk Institute.
   But then things took an unexpected turn – the researchers found new neurons actually impaired some types of working memory.
   “Working memory lasts a few seconds or minutes and those memories are then forgotten – like when you remember a phone number just long enough to dial it,” says Gael Malleret, Ph.D., the lead author with Dr. Saxe of the second paper, published in March in the Proceedings of the National Academy of Sciences.
   Dr. Malleret required the mice to remember the location of a food pellet for less than a minute, a brief memory akin to remembering a telephone number. He changed the pellet location in quick succession and found that mice without new neurons outperformed the other mice.
   “It was a bit of a surprise that taking neurons away improves memory,” Dr. Hen says. “All other studies until now have shown neurogenesis improves memory.”
   The new neurons may impair working memory because they simultaneously improve long-term memory. “As the trials proceed, the normal mice have turned their short-term memories into long-term memories. They can’t forget the locations of pellets from the previous trials and then they get confused,” Dr. Malleret says. “Sometimes remembering everything isn’t a good thing. We need to forget.”
   “How these results translate to humans is not clear right now,” Dr. Hen says. “We have to be cautious, therefore, in saying that a drug designed to improve memory in people will negatively impact another type of memory. The important take home message is: neurogenesis may have multiple functions.”

 —Susan Conova 

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