Assessment of neuronal number affected by reduction of an autism-risk gene in primary motor cortex dedicated to vocal learning

Abstract:

The zebra finch songbird is an excellent model for studying the neural mechanisms that influence vocal learning. Humans and zebra finches share the capacity for socially learned vocal communication. In the neural circuitry of songbird development, the primary cortical vocal control nucleus, robust nucleus of the arcopallium (RA), shares distinct similarities to the human laryngeal motor cortex area that controls speech. Male zebra finches retain high levels of the protein encoded by the autism-risk gene Contactin associated protein-like 2 (Cntnap2) during sensorimotor learning of their courtship song within the RA. In humans, mutations in CNTNAP2 are associated with speech impairments, Autism Spectrum Disorder, and cortical dysplasia-focal epilepsy. To understand the role of Cntnap2 specifically on vocal learning, we used RNA interfering constructs to reduce the high levels of Cntnap2 during the sensorimotor learning period. Sibling male zebra finches were assigned to three conditions: A control condition that received no RNA interfering construct; a control condition (AAV-shGEN) that received a random RNA interfering construct; and an experimental condition that received the Cntnap2 knock-down RNA interfering construct (AAV-KD). We are currently validating the number of neurons transfected with the virus which is critical in determining the relationship between song learning deficits to the specific effects of cntnap2 knock-down, rather than to non-specific effects. We hypothesize that the greater the number of cells transfected with the knock-down, the greater the learning deficits.