Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations

Abstract

Autism spectrum disorders (ASD) are characterized by impaired learning of culturally transmitted behaviors like social skills, speech, and language1-3. These behaviors are learned by copying parents and other social models during development, a two-stage process that involves forming memories of appropriate behaviors during social experiences and then using those memories to guide imitation. How ASD-linked genes impair these often-intertwined aspects of learning is not known, thereby limiting our understanding of the developmental progression of ASD and the targeting of therapeutic interventions. Here we show that these aspects of learning are dissociable and that the ASD-linked gene FoxP1 selectively impairs learning from social experience, but not behavioral imitation. Haploinsufficiency of FOXP1 in humans causes FOXP1 syndrome, a neurodevelopmental disorder typified by severe disruptions in speech and language development, and other ASD-associated symptoms4,5. We tested how knockdown of FoxP1 (FP1-KD) affects the cultural transmission of vocal behaviors in zebra finches, a songbird that learns by memorizing and vocally copying the song of an adult song-tutor. We find that FP1-KD blocks song learning in juvenile birds by selectively impairing their ability to encode a memory during social experiences with a songtutor. These learning deficits are linked to disruptions in experience-driven structural and functional plasticity. However, if birds are exposed to tutor-song prior to FP1-KD, their ability to imitate that song during development is unaffected. Thus, FP1-KD impairs cultural transmission of vocalizations by disrupting the ability to form appropriate vocal memories, yet spares the ability to use previously acquired memories to guide vocal learning. This indicates that learning from social experience may be particularly vulnerable in FOXP1 syndrome.