20 September 2010

Doh! Scientists uncover Homer Simpson gene

by Kate Melville

Deleting a certain gene in mice (one that is also found in humans) makes them smarter, but the Emory University researchers who discovered this so-called "Homer Simpson gene" are cautious about its potential to enhance cognition in humans, saying that very little is known about the mysterious region of the brain the gene is linked to.

Published in the Proceedings of the National Academy of Sciences, the findings show that mice with a disabled RGS14 gene are able to remember objects they'd explored and learn to navigate mazes better than regular mice, suggesting that RGS14's presence limits some forms of learning and memory. Since RGS14 appears to hold mice back mentally, the Emory researchers have been referring to it as the "Homer Simpson gene."

RGS14 is primarily turned on in the CA2 region of the hippocampus, a part of the brain known to be involved in consolidating new learning and forming new memories. However, the CA2 region lies off the beaten path scientifically and it's not clear what its functions are, say the researchers.

Interestingly, the CA2 region is distinct from other brain regions for being resistant to long-term potentiation (a strengthening of connections between neurons that can be seen after new memory formation), and neurons within CA2 are able to survive injury by seizures or stroke more than neurons in other parts of the hippocampus.

But in mice with a disabled RGS14 gene, the CA2 region was capable of "robust" long-term potentiation, meaning that in response to electrical stimulation, neurons there had stronger connections. On top of that, the ability of the gene-altered mice to recognize objects previously placed in their cages was enhanced, compared to normal mice. They also learned more quickly to navigate through a water maze to a hidden escape platform by remembering visual cues.

"A big question this research raises is why would we, or mice, have a gene that makes us less smart - a Homer Simpson gene?" researcher John Hepler posits. "I believe that we are not really seeing the full picture. RGS14 may be a key control gene in a part of the brain that, when missing or disabled, knocks brain signals important for learning and memory out of balance."

The researchers say the lack of RGS14 doesn't seem to hurt the altered mice, but it is still possible that they have their brain functions changed in a way that researchers have not yet been able to spot. Besides being resistant to injury by seizure, certain types of CA2 neurons are lost in schizophrenia, and loss of another gene turned on primarily in the CA2 region leads to altered social behaviors. "This suggests that these mice may not forget things as easily as other mice, or perhaps they have altered social behavior or sensitivity to seizures," Hepler said. "But not necessarily."

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Source: Emory University