Genetic studies have suggested an association between autism and mutation in a gene which codes for a protein called neuroligin. Neuroligins have been shown to mediate the formation of connections between brain cells and control the balance of activity between them. Preliminary studies in Dr. Powell's lab have suggested that one form of neuroligin plays a role in social learning and other autism-related behaviors in mice. These studies will be expanded to examine multiple mutations of different forms of neuroligins in an animal model, as well as investigate the functional effects of a mutation of a previously unstudied form of neuroligin (neuroligin 3). In parallel with studies which examine the behavioral function, collaborators on this project will be directly examining the molecular function of neuroligins in the brain using electrophysiology, biochemistry, and imaging techniques. These studies will provide a better understanding of how neuroligin mutations might lead to autism-like behavioral abnormalities, and lead to a better understanding of the basic neurobiological underpinnings of autism. Significance: It is anticipated that these studies will lead to one or more novel animal models of autism. Once autism-related behavioral abnormalities have been fully characterized, there will be a unique opportunity to use our knowledge of neuroligin function to test potential treatments in neuroligin-based mouse models of autism.