Deleting a gene creates super-smart mice...and maybe humans too

Switching off a single gene in mice unlocks a part of their brain that is otherwise inactive, boosting learning and memory. The same gene seems to serve a similar purpose in humans, creating hope that humans could enjoy similar benefits.

The RGS14 gene has been the subject of intense scrutiny by researchers since its discovery ten years ago. A study last year suggested increased RGS14 levels could greatly aid recall, but pharmacologist John Hepler and his colleagues at Emory University are so convinced the gene is holding mice's brains back that they've nicknamed it the "Homer Simpson gene." (This is of course completely different from the Simpson gene, which causes a process of dumbening in Simpson males.)

The protein created by RGS14 is thought to be crucial to processing various signals needed to create memories. RGS14 is mostly found in a part of the hippocampus known as CA2, a part of the brain researchers still know very little about. We know that the hippocampus helps consolidate learning and retain new memories, but the specific functions of the CA2 region in particular has remained a mystery.

In order to better understand what RGS14 does, Hepler's research team disabled the RGS14 in a population of mice. They then studied how the CA2 region responded to electrical simulation in these particular mice. They found that the CA2 area was suddenly capable of long-term potentation, a process by which neural connections are strengthened and thus learning and memory creation are increased. In normal cases, the CA2 region doesn't undergo this process, which means it's of no use in memory creation but does make it more resistant to strokes and seizures.

But in the gene-altered mice, the CA2 region was now home to robust long-term potentation, and the external effects were obvious. The mice were now better at remembering and recognizing objects that had been placed in their cages, and they could more quickly navigate water mazes that depended on remembering visual hints.

This suggests switching off RGS14 could have great benefits to cognition, but Hepler is cautious in this assessment:

"A big question this research raises is why would we, or mice, have a gene that makes us less smart – a Homer Simpson gene? 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."

Still, they have yet to find any negative side-effects to deleting the gene. Besides offering some neural protection in the case of seizure or stroke, CA2 is linked to schizophrenia and certain forms of altered social behavior, although again those links aren't clear. The researchers are going to look more closely for what these gene-altered mice are losing when RGS14 is switched off, even if these effects have so far eluded detection.

Either way, the ultimate goal of this is understandably ambitious, as the researchers think this really could be a way to boost learning and memory in humans:

"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. But not necessarily. The pipe dream is that maybe you could find a compound that inhibits RGS14 or shuts it down," he adds. "Then, perhaps, you could enhance cognition."

[Proceedings of the National Academy of Sciences]