Jahel Guadardo
Home Institution: UCLA
UCLA Mentor: Dr. Stephanie A. White
Program: Deans Award
Abstract:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder has many genes that contribute to its phenotype. One such gene is Contactin-associated protein like 2 (CNTNAP2), which has been linked to ASD and abnormal language development. Rodent models that lack cntnap2 recapitulate some core phenotypes of ASD but fail to demonstrate abnormal vocal learning since rodent vocalizations are innate. Zebra finches, however, are a robust model for vocal learning and, by analogy, speech. The cortical song control region known as the robust nucleus of the acropallium (RA) is enriched with Cntnap2, which mirrors its enrichment in language areas in humans. Thus, we hypothesize that reduction of the Cntnap2 transcript in the RA of male juvenile zebra finches will lead to vocal imitation deficits. To investigate this, we introduced an interfering RNA to the RA through viral injection at the beginning of sensorimotor critical period for song learning and tracked song development. An important validation step is to determine whether the results were a product of knocking down Cntnap2 or due to cell death. To determine this, I quantified levels of Cntnap2 and Casp3, a marker for cell death, in zebra finches. We demonstrated that reduction in Cntnap2 led to vocal imitation deficits. Ongoing experiments are aimed at ascertaining whether this is due to the experimental manipulation or to cell death. The results will clarify Cntnap2’s role in vocal imitation accuracy in RA. Understanding the mechanisms by which Cntnap2 affects vocal imitation in zebra finches could have implications for understanding its mechanism in human speech.