Knocking Out a 'Dumb' Gene Boosts Memory in Mice

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?"