Alterations in synaptic connectivity and dendritic morphology are associated with neuro-developmental disorders including autism. Mutations in the Neuroligin-3 protein are associated with autism-spectrum disorders in some families. The neuronal aberrations caused by these mutations represent a model for understanding the cellular basis of autistic disorders. We have analyzed the consequences of the disease-associated mutation in neuroligin-3 in vitro and discovered that it results in a defect in protein transport. In ongoing studies we are examining the alterations in synaptic wiring in mice carrying the autism-associated mutation in the Neuroligin-3 gene. This work is further complemented with conditional mouse models, that allow us to reversibly inactivate or overexpress Neuroligin-3 in specific neuronal populations. By learning more about how Neuroligins and specifically Neuroligin-3 contribute to the normal development of synaptic circuits we hope to understand the cellular and circuit level defects that underlie autism-spectrum disorders. This knowledge should prove valuable for identifying strategies to treat these disorders in the future.