UCLA

Autism spectrum disorder (ASD) is characterized by impairment in social communication along with additional endophenotypes. Songbirds offer a relevant animal model for investigating communication deficits because like humans, but unlike most mammalian research models, a substantial portion of their communication signals are learned using similar cortical-striatal circuitry. Cyclic-AMP-Regulated Phosphoprotein 21kDa (ARPP21) is the host gene of miRNA-128 that has been associated with ASD. Computational models suggest that the collaboration between ARPP21 and Protein Phosphatase 1 Regulatory Inhibitor Subunit 1B (PPP1R1B, or DARPP32) can enhance cortical-striatal synaptic strength through the activation of CaMKII. Previous work has demonstrated enhanced song learning through inhibiting miRNA-128 within Area X, the song-dedicated region of the songbird striatum. Follow-up work discovered a downregulation of a striatal gene co-expression module following two hours of morning singing in a cluster of ARPP21-expressing medium spiny neurons. Together, these findings suggest a role for the miR-128 host gene, ARPP21, in learned vocalizations. Yet, the potential link between ARPP21 expression levels and vocal learning in songbirds and humans remains unexplored. The present investigation aimed to determine whether ARPP21 and DARPP32 proteins are co-expressed in a subset of medium spiny neurons in the striatal Area X of adult male zebra finches. The results provide biological support for the computational model mentioned above. Additionally, they may reveal whether the co-expression of ARPP21 and DARPP32 is associated with vocal learning in both songbirds and humans.