Mice reveal clues to the basis of human speech

Human speech requires complex rapid movements of mouth and facial muscles, learned during our early years. Now, research in mice has linked a rare inherited human speech and language disorder to fundamental deficits in learning to make sequences of movements, suggesting that the brain circuits involved in this type of learning are crucial for human speech development.

The human disorder, caused by mutation of the FOXP2 gene, is characterised by disruptions of speech and written language. Difficulties with speaking are thought to be down to problems with learning and/or producing the facial muscle movements needed for speech.

But now Dr Simon E Fisher at the Wellcome Trust Centre for Human Genetics in Oxford and colleagues have found that a mutation in the equivalent gene in mice (Foxp2) causes more general problems with learning of rapid movement sequences when running on wheels or balancing on rotating rods.

Unlike many inherited speech disorders (which involve changes in numerous genes), a mutation at a single DNA base in FOXP2 is enough to cause this condition in humans. This means that scientists can 'knock out' or mutate this gene in animals to produce a model of the human disease, allowing them to investigate what's happening in the brain.

The researchers produced mice carrying one normal copy of Foxp2 and one mutated version - matching a genetic change observed in affected humans. These mice developed normally in terms of the basics of making and controlling movements, but they had trouble building on these so-called motor skills, for example, taking longer to learn how to run faster and further on a tilted running track.

Further evidence of problems with learning came when the researchers looked at the brain circuits where Foxp2 is known to be active. The way the connections between nerve cells are strengthened or weakened - which is vital for learning - was abnormal in mice carrying the mutated gene.

These findings add weight to the idea that human speech development relies on evolutionarily ancient brain circuits involved in learning of motor skills.

The differences seen between the effects of Foxp2 mutations in mice and FOXP2 mutations in humans raise several interesting questions. Does FOXP2have a different role in humans than it does in mice, or could it be that the gene is involved in learning an animal's most demanding motor skills, which may for humans - but not mice - be speech?

The team has also generated mice in which Foxp2 can be 'switched off' in particular parts of the brain, and is now using these to understand more how different brain regions are involved in the learning problems revealed in this study.

Groszer M et al. Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.  Curr Biol. 2008 Mar 11;18(5):354-62.