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Mice carrying a human version of the speech gene FOXP2 show their smarts in maze studies.

Mice carrying a human version of the speech gene FOXP2 show their smarts in maze studies.

Henry F. Hall and Jannifer Lee

Human speech gene can speed learning in mice

"What's for dinner?" The words roll off the tongue without even thinking about it—for adults, at least. But how do humans learn to speak as children? Now, a new study in mice shows how a gene, called FOXP2, implicated in a language disorder may have changed between humans and chimps to make learning to speak possible—or at least a little easier.

As a uniquely human trait, language has long baffled evolutionary biologists. Not until FOXP2 was linked to a genetic disorder that caused problems in forming words could they even begin to study language’s roots in our genes. Soon after that discovery, a team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, discovered that just two bases, the letters that make up DNA, distinguished the human and chimp versions of FOXP2. To try to determine how those changes influenced the gene's function, that group put the human version of the gene in mice. In 2009, they observed that these "humanized" mice produced more frequent and complex alarm calls, suggesting the human mutations may have been involved in the evolution of more complex speech.

Another study showed that humanized mice have different activity in the part of the brain called the striatum, which is involved in learning, among other tasks. But the details of how the human FOXP2 mutations might affect real-world learning remained murky. To solve the mystery, the Max Planck researchers sent graduate student Christiane Schreiweis to work with Ann Graybiel, a neuroscientist at the Massachusetts Institute of Technology in Cambridge. She's an expert in testing mouse smarts by seeing how quickly they can learn to find rewards in mazes.

In humans and other animals, learning occurs in two ways, Graybiel explains. The first requires breaking the task at hand into distinct steps and performing them one at a time. For example, to learn to ride a bike, you first need to remember to hold the handlebars straight, then to put your feet on the pedals, and finally push with your legs to make the pedals go around. At some point, though, these step-by-step movements become habit and you switch to the second type of learning, which is based on unconscious repetition. Now, your bike riding improves simply by repeating the task, rather than thinking through each step.

To figure out which type of learning may have been aided by the changes in the human version of FOXP2, Schreiweis tested humanized mice in mazes. In some cases, the mice were required to remember that turning right always led to a reward, indicating that they had acquired the repetitive habit of turning right and their skill had become “unconscious.” In other cases, they had to look around and figure out that the reward was always on the east arm of the maze, a task that required the behavioral flexibility of step-by-step learning. That’s because, depending on where in the maze the mouse started, it had to look around to figure out where to go.

When humanized mice and wild mice were put in mazes that engaged both types of learning, the humanized mice mastered the route to the reward faster than their wild counterparts, report Schreiweis, Graybiel, and their colleagues online today in the Proceedings of the National Academy of Sciences. But when the mice were engaged in just one type of learning, humanized and wild mice did equally well on all the tests. That was unexpected; the researchers forecast that the humanized mice would have some advantage in at least one of the learning types.

When other scientists tried to repeat the maze trials that showed a difference between the wild and humanized mice, however, they, too, found no difference in learning abilities. "It was very fascinating but a bit frustrating, too," Graybiel recalls.

She began to wonder if the improvement they saw initially was related to interactions between the two types of learning. The team also realized that Schreiweis had set up her mazes in a crowded lab full of computers, lab benches, and wall posters that the mice could turn to for clues about their location in the maze. In contrast, the other teams had done their tests in less cluttered, or even empty, rooms.

When Schreiweis and her colleagues put their mazes back in a crowded room, the humanized mice excelled once again. Furthermore, in yet another series of tests, they demonstrated that humanized mice that had already been trained in step-by-step learning were more readily able to switch to repetitive learning. And cellular studies bolstered this conclusion: Each type of learning involves a different part of the striatum, and the part for learning by repetition was more primed for action in the humanized mouse.

The results suggest the human version of the FOXP2 gene may enable a quick switch to repetitive learning—an ability that could have helped infants 200,000 years ago better communicate with their parents. Better communication might have increased their odds of survival and enabled the new version of FOXP2 to spread throughout the entire human population, suggests Björn Brembs, a neurobiologist at the University of Regensburg in Germany, who was not involved with the work.

"The findings fit well with what we already knew about FOXP2 but, importantly, bridge the gap between behavioral, genetic, and evolutionary knowledge," says Dianne Newbury, a geneticist at the Wellcome Trust Centre for Human Genetics in Oxford, U.K., who was not involved with the new research. "They help us to understand how the FOXP2 gene might have been important in the evolution of the human brain and direct us towards neural mechanisms that play a role in speech and language acquisition."

Faraneh Vargha-Khadem, a cognitive neuroscientist at University College London who was not involved with the work, also applauds the study but is not sure how relevant the findings are to speech in particular. In the maze experiments, mice depend on visual cues to figure out what to do, whereas infants are responding to audio cues. "If you really want to deal with the right [brain] circuit, you have to work with the right stimuli," she says.

Study co-author Simon Fisher of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, emphasizes that FOXP2 is just one piece of this evolutionary puzzle. "It is clear that our human speech and language capacities involve many different genes, interacting in complex networks, so there will never be an explanation of our unique ability in terms of just a single molecule."