Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Background - Autism spectrum disorders (ASDs) are neuro-developmental disorders characterized by impairments in social interactions, language development, and emotion reactivity. The initial behavioural signs of ASDs often appear during the first year of life, and mounting evidence supports that the origin in altered developmental processes involving synaptic and dendritic organizations. Neuronal circuits are complex, they are wired up with 100s of billions of brain neurons to form trillion of accurate synapses, and failure of these connections can often lead to devastating developmental neurological disorders, such as ASDs. A recent breakthrough in the genetic basis of ASDs has been reported in a study identifying mutations in the neuroligin genes, NLGN3 and NLGN4 in ASDs patients from a Swedish family. Thus, understanding the nature of neuroligin on normal brain development and how mutation of this gene can impair circuit function that lead to ASDs is critically important. Method - Our laboratory utilizes albino Xenopus laevis tadpoles as a system to examine dendritic growth and neuronal circuit function, in vivo, within an intact and un-anaesthetized developing brain. Xenopus laevis is widely used in neuro-developmental research due to the high degree of similarity of its fundamental neurobiology with higher vertebrates. Using single-cell electroporation, we can genetically manipulate individual neurons in the brain, and monitor the effect of the manipulation on the particular developing neurons in the immature brain. We will be able to monitor the effect of mutation in neuroligin on both the growth and the functional response of an individual neuron in the brain in vivo. Significance - We proposed a powerful in vivo model that can directly examine the possible cause of ASDs and provide evidence to show how neuroligin mutations may disrupt brain circuit formation.