It is important to develop laboratory based models of autism, since such models can be readily used to generate and test hypotheses and to investigate, characterize, and manipulate biological mechanisms in much more detail that would be possible using human subjects. Drosophila, the fruit fly, is such an advantageous experimental model and a high throughput system. The present study plans to create the Drosophila equivalent of the genetic abnormalities that underlie syndromes such as Rubinstein-Taybi syndrome, neurofibromatosis type 1, tuberous sclerosis complex type 1, tuberous sclerosis complex type 2 and Rett syndrome – all of which are associated with autism spectrum disorders. The study will also examine any additional impact of a combination of one of these genes plus the FMR1 (fragile X) gene. The study will examine what effects such genetic manipulations have on biochemical pathways in the brain and how this relates to behaviors. The social and memory aspects of Drosophila courtship will be used as surrogate markers for impairments in social interactions and cognitive ability in autism. Alterations in the architecture of the brain areas that control these Drosophila behaviors will also be examined. Furthermore, the research seeks to identify pharmacological agents that can rescue the phenotype.