Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2. Do special “human” genes provide the biological substrate for uniquely human traits, such as language? Genetic aberrations of the human FoxP2 gene impair speech production and comprehension, yet the relative contributions of FoxP2 to brain development and function are unknown. Songbirds are a useful model to address this because, like human youngsters, they learn to vocalize by imitating the sounds of their elders. Previously, we found that when young zebra finches learn to sing or when adult canaries change their song seasonally, FoxP2 is up-regulated in Area X, a brain region important for song plasticity. Here, we reduced FoxP2 levels in Area X before zebra finches started to learn their song, using virus-mediated RNA interference for the first time in songbird brains. Birds with experimentally lowered levels of FoxP2 imitated their tutor's song imprecisely and sang more variably than controls. FoxP2 thus appears to be critical for proper song development. These results suggest that humans and birds may employ similar molecular substrates for vocal learning, which can now be further analyzed in an experimental animal system.