Defects in oral communication are associated with many neurological disorders, including Huntington's disease. Despite their prevalence, the underlying causes of these communication deficits remain unclear. Using zebra finch song birds and transgenics, researchers at Rockefeller University (New York, NY) have established an important link between mHTT, a gene known to cause Huntington's disease in humans, and vocal communication (Nat. Neurosci. 18, 1617–1622; 2015).

Zebra finches are a popular model system for scientists studying language and communication. Zebra finches learn songs by mimicking the song of a 'tutor', or adult finch, similar to the way human children acquire language from their parents. Additionally, the brain circuitry required for vocal learning in songbirds is similar to that of humans. “There hasn't been a good animal model for any kind of speech disorder,” stated lead author Wan-Chun Liu in a press release. “Rats and mice, the most common lab animals, can't tell us much about speech disorders, since their vocalizations are innate, not learned. That's what makes songbirds so special.” Liu and colleagues generated transgenic finches harboring mHTT and examined the effects on vocal communication. By analyzing the songs of these mutant birds, they found that compared to wild-type zebra finches, the transgenic mutants displayed a notable defect in song learning.

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Their songs contained incorrect syllables, long repeats and stuttering, and these defects worsened with age. These findings suggest that the neuronal circuits responsible for song learning were not intact in mHTT mutants. To test this hypothesis, the authors created lesions in areas of the brain known to have a role in song learning. Although lesions to these brain circuits typically have no effect on singing in wild-type zebra finches, they caused significant impairments to song production in mHTT zebra finches, suggesting that the song learning circuitry never correctly developed. Mutant songbirds also showed neuropathology similar to that seen in Huntington's disease, including decreased expression of dopamine and androgen receptors and the presence of mHTT protein aggregates in the brain. The authors propose that these abnormalities could have contributed to the impaired song production.

Liu noted the far-reaching implications of this study: “Our work has relevance beyond Huntington's. By creating the first song bird models for vocal degeneration, we have achieved what I believe is a turning point for all kinds of diseases that affect speech, like Alzheimer's, Parkinson's, and autism.”