Abstract
The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. FOXP2 mutations are associated with specific speech and language impairments. In songbirds, experimentally altered FoxP2 expression levels in the striatal song nucleus Area X impair vocal learning and song production. Overall FoxP2 protein levels in Area X are low in adult zebra finches and decrease further with singing. However, some Area X medium spiny neurons (MSNs) express FoxP2 at high levels (FoxP2high MSNs) and singing does not change this. Because Area X receives many new neurons throughout adulthood, we hypothesized that the FoxP2high MSNs are newly recruited neurons, not yet integrated into the local Area X circuitry and thus not active during singing. Contrary to our expectation, FoxP2 protein levels did not predict whether new MSNs were active during singing, assayed via immediate early gene expression. However, new FoxP2high MSNs had more complex dendrites, higher spine density and more mushroom spines than new FoxP2low MSNs. In addition, FoxP2 expression levels correlated positively with nucleus size of new MSNs. Together, our data suggest that dynamic FoxP2 levels in new MSNs shape their morphology during maturation and their incorporation into a neural circuit that enables the maintenance and social modulation of adult birdsong.
Highlights
The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits
We found that FoxP2 expression in Area X was very variable, with some neurons expressing FoxP2 at high levels and some at low levels (Fig. 1c)
Because we were interested in the two extremes of the expression levels in this study, we did not analyze the new neurons with intermediate FoxP2 expression levels further (29.3% ± 9.4, SD, see Methods)
Summary
The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. Genetic manipulations of FoxP2 expression levels in the striatal song nucleus Area X during the critical phase of song learning lead to inaccurate and incomplete imitation of the tutor’s song and more variable vocal production[3,8,9,10] This phenotype bears similarities to the specific speech deficits called developmental verbal dyspraxia, DVD (or childhood apraxia of speech), that patients carrying FOXP2 mutations suffer from. In mice carrying humanized Foxp[2] alleles (Foxp2hum/hum mice), Foxp2high MSNs are more numerous in the dorsal striatum and their MSNs have longer dendrites than wildtype mice[36,37] Based on the latter results we hypothesized that FoxP2 levels of new MSNs in adult songbirds correlate with their neural morphology. We virally labelled neural progenitors and analyzed their FoxP2 expression, dendrite complexity and spine density after migration into Area X
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