TY - JOUR T1 - Beyond critical period learning: Striatal FoxP2 affects the active maintenance of learned vocalizations in adulthood JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0071-19.2019 SP - ENEURO.0071-19.2019 AU - Nancy F. Day AU - Taylor G. Hobbs AU - Jonathan B. Heston AU - Stephanie A. White Y1 - 2019/03/22 UR - http://www.eneuro.org/content/early/2019/03/22/ENEURO.0071-19.2019.abstract N2 - In humans, mutations in the transcription factor FOXP2 result in language disorders associated with altered striatal structure. Like speech, birdsong is learned through social interactions during maturational critical periods, and relies on auditory feedback during initial learning and on-going maintenance. Hearing loss causes learned vocalizations to deteriorate in adult humans and songbirds. In the adult songbird brain, most FoxP2-enriched regions (e.g. cortex, thalamus) show a static expression level, but in the striatal song control nucleus, Area X, FoxP2 is regulated by singing and social context: When juveniles and adults sing alone, its levels drop, and songs are more variable. When males sing to females, FoxP2 levels remain high and songs are relatively stable: This ‘on-line’ regulation implicates FoxP2 in ongoing vocal processes, but its role in the auditory-based maintenance of learned vocalization has not been examined. To test this, we overexpressed FoxP2 in both hearing and deafened adult zebra finches and assessed effects on song sung alone versus songs directed to females. In intact birds singing alone, no changes were detected between songs of males expressing FoxP2 or a GFP construct in Area X, consistent with the marked stability of mature song in this species. In contrast, songs of males overexpressing FoxP2 became more variable and were less preferable to females, unlike responses to songs of GFP-expressing control males. In deafened birds, song deteriorated more rapidly following FoxP2 overexpression relative to GFP controls. Together, these experiments suggest that behavior-driven FoxP2 expression and auditory feedback interact to precisely maintain learned vocalizations.Significance Statement Mutations within the FOXP2 gene impair speech and language. In zebra finch songbirds, the predominant model for investigating the neural and genetic mechanisms underlying human speech, FoxP2 is critical for song learning. Striatal FoxP2 expression levels correlate with song variability. We overexpressed FoxP2 in the striatopallidum of adult male zebra finches to assess its contribution to the maintenance of adult vocalizations independent of developmental perturbations. We tested the hypothesis that high FoxP2 expression promotes song stability by longitudinally assessing song in the presence and absence of auditory feedback and in two social contexts. We found that dysregulated FoxP2 interferes with hearing-dependent song maintenance. These results suggest that auditory-based regulation of FoxP2 is critical for the ongoing maintenance of adult vocalizations. ER -