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Knocking Out a "Dumb" Gene Boosts Memory in Mice














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We like to think of our brain as an incredibly sophisticated thinking machine that has been fine-tuned by evolution. But recently researchers working with mice found that a tiny genetic manipulation significantly boosted brainpower with seemingly no negative consequences. People have this gene, too, and it is active in the same brain area. In other words, we may have a gene in our heads that is actively making us dumber.

Emory University pharmacologist John Hepler and his team studied a section of the hippocampus called CA2, found in both mice and humans. Although the hippocampus is crucial for memory, the neurons in CA2, oddly, fail to participate in the cellular process on which learning and memory depend: long-term potentiation, which strengthens communication between neurons that fire together.

The researchers noticed that the neurons in CA2 were saturated with RGS14, a signaling protein that mysteriously inhibits long-term potentiation. When the investigators bred mice lacking the gene that codes for RGS14, they found that the neurons in CA2 suddenly demonstrated long-term potentiation.

The genetic tweak affected more than physiology—it changed how the mice performed on memory tests, too. The experimenters presented two identical objects to knock­out mice, which lacked the RGS14 gene, and to normal mice. Four hours and again 24 hours later, the researchers switched one of the objects with a new object. The knockout mice spent far more time exploring the new object than the normal mice did, indicating that the altered rodents had a better memory for distinguishing familiar and strange objects. Knockout mice also learned to navigate a water maze and locate a submerged platform faster than normal mice did. The scientists observed no detriments from removing the RGS14 gene.

“Why would we have a gene that makes us dumber?” asks Serena Dudek, a neuroscientist at the National Institute of Environmental Health Sciences and a co-author of the study, which was published in the September issue of the Proceedings of the National Academy of Sciences USA. “We don’t know. But if the gene is conserved by natural selection, there must be some reason. Intuitively, it seems there should be a downside to having this gene knocked out, but we haven’t found it so far. It may be that these mice are hallucinating, and you just can’t tell.”

Alcino Silva, a neurobiologist at the University of Cali­fornia, Los Angeles, and an expert on the biology of memory enhancement who was not involved in the new study, agrees. “My suspicion is when you enhance one thing, you cause deficits in others,” Silva says.

Despite their suspicions that the consequences of disabling this gene will materialize eventually, both Silva and Dudek see theraputic potential: the RGS14 gene and protein are now promising future targets of treatments for learning and memory disabilities.

Editor's note: The original print title was "Handicapped by Our Genes?"


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  1. 1. jabralnoaimi 12:09 AM 1/21/11

    Possible reasons for why gene for RGS14 was conserved by natural selection:

    1-Knockout or clever mice spent more time exploring new objects. This could be detrimental in the wild wher the search for food and security are of primary importance.

    2-There is no selective pressure for mice that that solve complicated problems such as navigating water mazes because such problems are not usually found in the wild.

    Jabr Alnoaimi
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  2. 2. jimg3525 10:07 AM 2/15/11

    Not all genetic problems are eliminated by natural selection.

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  3. 3. tharter 10:27 AM 2/15/11

    Something like Jabr's #1 could very easily be true. It could be more subtle than that though. For instance the resulting neural architecture could be less flexible in the long run. Maybe they have trouble forgetting things they should forget too. Hard to say. However if the gene is conserved in species as disparate as humans and mice there would likely be a fairly basic reason.

    #2 I don't think works though Jabr. Mice are good at solving these kinds of problems presumably because they ARE similar to problems they face fairly often in real life and thus get selected for.

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  4. 4. suitti 12:42 PM 2/15/11

    The quick (and ethical) next thing to do is to see if there are humans with a switched off or faulty RGS14. If they exist in decent numbers, we might learn if it helps, has side effects, and so on. If you're only looking for one gene, it might be a relatively cheap study.

    There was, as i recall, a Russian journalist who remembered everything, seemingly forever. Said to be not too bright, and it caused lots of issues in later life. So, i could see a down side.

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  5. 5. rabbitgod 12:53 PM 2/15/11

    Who here has read flowers for algernon?

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  6. 6. letxequalx in reply to rabbitgod 06:52 PM 2/15/11

    It seems that it doesn't improve all cognitive functions but just those involving the formation of new memories- that's an important part of the game but not the whole game. Perhaps they could create an antigen that would render RGS14 inert? The possibility of someday improving the memory and learning ability in humans is very exciting.

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  7. 7. letxequalx in reply to jabralnoaimi 07:08 PM 2/15/11

    Intelligence is being redefined- it seems more and more likely that language and tool-using has been around a very long time. I think that in more recent epochs intelligence has proven a more effective strategy for survival. In conditions where resources are plentiful maybe the best strategy is to simply out breed other species. Where survival is more complex than simple over breeding it could be advantageous for the specie to 'invest' in learning. Perhaps this is a switch that has been turned off and on many times in natural history.

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  8. 8. JDahiya in reply to rabbitgod 02:29 AM 3/3/11

    Yep, and it reminded me also of Beggars in Spain (Nancy Kress). Maybe it prevents people/mice from being hunted down by other people/mice. Or a mating benefit, you know, like the reason many college-age girls act dumber than their boyfriends.

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