Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches

Abstract

The search for molecular underpinnings of human vocal communication has focused on genes encoding forkhead-box transcription factors, as rare disruptions of FOXP1, 2 and 4 have been linked to disorders involving speech and language deficits. In male songbirds, an animal model for vocal learning, experimentally altered expression levels of these transcription factors impair song production learning. The relative contributions of auditory processing, motor function or auditory-motor integration to the deficits observed after different FoxP manipulations in songbirds are unknown. To examine the potential effects on auditory learning and development, we focused on female zebra finches (Taeniopygia guttata) that do not sing but develop song memories, which can be assayed in operant preference tests. We tested whether the relatively high levels ofFoxP1expression in forebrain areas implicated in female song preference learning are crucial for the development and/or maintenance of this behaviour. Juvenile and adult female zebra finches received FoxP1 knockdowns targeted to HVC (proper name) or to the caudomedial mesopallium (CMM). Irrespective of target site and whether the knockdown took place before (juveniles) or after (adults) the sensitive phase for song memorisation, all groups preferred their tutor’s song. However, adult females with FoxP1 knockdowns targeted at HVC showed weaker motivation to hear song and weaker song preferences than sham-treated controls, while no such differences were observed after knockdowns in CMM or in juveniles. In summary, FoxP1 knockdowns in the cortical song nucleus HVC were not associated with impaired tutor song memory but reduced motivation to actively request tutor songs.Significance statementVocal production learning in humans and birds requires auditory memory formation and recall. HumanFOXP1mutations are associated with broad neurodevelopmental disorders including speech and language impairments. In juvenile male zebra finches knockdowns of the avian ortholog, FoxP1, in regions relevant for song learning impair song copying. Whether FoxP1 is relevant for auditory learning is unknown. Studies in non-singing females make it possible to test this. We report that FoxP1 knockdowns in CMM during development and adulthood do not affect auditory learning, while knockdowns in the premotor nucleus HVC in adult but not juvenile female zebra finches reduce tutor song preference and motivation to receive playbacks. These findings support roles of FoxP1 in auditory perception and motivation to hear song.