'Homer' gene limits mouse memory


Deleting a certain gene in mice can make them smarter by unlocking a mysterious region of the brain.

Mice with a disabled RGS14 gene are able to remember objects they had previously explored and learn to navigate mazes better than regular mice, suggesting that the gene’s presence limits some forms of learning and memory. Since RGS14 appears to hold mice back mentally, Emory pharmacologist John Hepler and his colleagues have dubbed it the “Homer Simpson gene.”

RGS14 regulates several molecules that process brain signals known to be important for learning and memory. RGS14 is primarily turned on in one particular part—the CA2—of the hippocampus, a region of the brain known to consolidate new learning and form new memories. But very little is known about the CA2 region, says Hepler.

Neurons in the hippocampus will strengthen their connection after a new memory forms, but CA2 neurons do not. The loss of certain CA2 neurons is known to play a role in schizophrenia.

Hepler and his team were surprised to find that, in mice with a disabled RGS14 gene, the CA2 region was capable of robust long-term potentiation. In response to electrical stimulation, neurons there had stronger connections.

“A big question this research raises is why would we have a gene that makes us less smart?” Hepler says. “I believe that we are not really seeing the full picture. RGS14 may be a key gene that, when missing or disabled, knocks brain signals important for learning and memory out of balance.”—Quinn Eastman

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Emory Medicine Winter 2011