Human Gene Helps Mice Learn Faster

 Genetics  

Researchers have shown that the human version of a gene called FOXP2 makes it easier to transform new experiences into routine procedures. When they engineered mice to express humanized FOXP2, the mice learned to run a maze much more quickly than normal mice.

Mice that receive a human version of a speech and language gene display accelerated learning, according to a new study.

While the researchers are careful not to call this an uplift gene, the work reveals something new and fascinating about the evolution of human speech and language.

The gene for the protein called FOXP2 has been firmly linked to human speech and language. Humans with just one functional copy of this gene experience difficulties in learning and struggle with spoken and written language.

The investigators discovered the mice with the human form of FOXP2 learned profoundly faster than regular mice when both declarative and procedural forms of learning were involved. The scientists published their findings in the Proceedings of the National Academy of Sciences.

The findings suggest that FOXP2 may help humans with a key component of learning language -- transforming experiences, such as hearing the word "glass" when we are shown a glass of water, into a nearly automatic association of that word with objects that look and function like glasses, says Ann Graybiel, an MIT Institute Professor, member of MIT's McGovern Institute for Brain Research, and a senior author of the study.

"This really is an important brick in the wall saying that the form of the gene that allowed us to speak may have something to do with a special kind of learning, which takes us from having to make conscious associations in order to act to a nearly automatic-pilot way of acting based on the cues around us."

“This really is an important brick in the wall saying that the form of the gene that allowed us to speak may have something to do with a special kind of learning, which takes us from having to make conscious associations in order to act to a nearly automatic-pilot way of acting based on the cues around us,” Graybiel says.

The gene itself is not unique—chimps have a version of it. But because the human and chimpanzee lineages diverged roughly 6 million years ago, they don't have two key changes in amino acids that humans have evolved.

To learn more about how FOXP2 alters the brain, scientists genetically engineered mice with the human form of FOXP2. In experiments with these rodents, the researchers focused on two modes of learning thought to be crucial for speech and language—declarative learning, which involves knowledge learned consciously, and procedural learning, which involves knowledge learned by experiencing something enough times for it to become habit.

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The scientists had mice run through a maze to get a reward of chocolate milk. The animals could figure out the location of the reward either through sensory cues such as rough or smooth floors, which corresponds to declarative learning. Or, they could discover the reward was always linked to either a left or right turn, which corresponds to procedural learning.

Declarative learning involves circuits in the central part of the striatum region of the brain, while procedural learning involves circuits in more peripheral parts of the striatum. The scientists found that both sets of circuits were altered in the mice with the human form of FOXP2.

Prior studies found that mice with the human version of FOXP2 demonstrate profound changes in the chemistry and anatomy of brain circuits essential for acquiring habits and other physical and mental behaviors, such as songbirds learning song. The kinds of changes seen in these studies may once have helped the human brain evolve speech and language.

"I don't think the goal is to make smarter animals, but rather to dissect out the biology underlying smartness," Smith says. "Having said that, if we can find a procedure like this that would help treat neurological or psychiatric disorders, that would be a wonderful purpose. For example, Parkinson's disease involves the same brain circuits being studied in this article — perhaps genes could be tweaked in similar ways to help."

This study "provides new ways to think about the evolution of Foxp2 function in the brain," says Genevieve Konopka, an assistant professor of neuroscience at the University of Texas Southwestern Medical Center who was not involved in the research. "It suggests that human Foxp2 facilitates learning that has been conducive for the emergence of speech and language in humans. The observed differences in dopamine levels and long-term depression in a region-specific manner are also striking and begin to provide mechanistic details of how the molecular evolution of one gene might lead to alterations in behavior."


SOURCE  MIT

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