Posted April 8, 2015
Stephanie A. White, Ph.D., University of California, Los Angeles
Autism spectrum disorder (ASD) are a range of neurodevelopmental disorders characterized by social and communication deficits, repetitive behaviors, sensory issues, and cognitive delays. Many children with ASD experience significant language delays and do not begin to speak until much later than typically developing children. Although several animal models have been developed that display the characteristics of ASD, including repetitive behavioral and social deficits, no models exist to study vocal learning and the communication difficulties that are fundamental hurdles to children with ASD. This is largely due to the fact that vocal learning is rare in the animal kingdom and is so far found only in bats, cetaceans (whales, dolphins, and porpoises), elephants, seals, and songbirds. Dr. Stephanie White, of the University of California, Los Angeles, sought to develop a novel model of ASD using the zebra finch songbird to study learned vocal communication. The zebra finch songbird serves as a unique model to study vocal learning because only the male songbirds sing and the females do not, allowing investigation into the genes that may differ between the two and control vocal learning.
With support from a Fiscal Year 2009 ARP Idea Award, Dr. White and her research team found that a key region of the brain song control system in songbirds known as the robust nucleus of the arcopallium (RA) has increased expression of a gene called contactin-associated protein-like 2 (Cntnap2). Mutations in the Cntnap2 gene are associated with language-related disorders in humans, including ASD. Interestingly, in the songbirds, this gene was highly expressed in the male songbirds, who sing, at the onset of the sensorimotor phase of song learning, and was much lower in the females, who do not sing, during this same time period. Dr. White also found that a gene called Forkhead Box P2 (FOXP2), which is a known gene involved in speech disorders and directly interacts with Cntnap2, is also expressed in the male RA. Additionally, Dr. White further defined the exact timing and location within the RA where Cntnap2 levels increase in male songbirds, providing important information for testing intervention strategies that may alter behavioral outcomes.
Dr. White is currently testing inhibitors of Cntnap2 on behavioral effects of song learning in the zebra finch songbird model. Her work thus far further defines the role of Cntnap2 and FOXP2 in the vocal learning of the zebra finch songbird and provides strong evidence for additional use of this animal model to study the vocal learning deficits associated with ASD.
Condro M and White S. 2013. Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning. J Comp Neurol 522(1):169-185.