Autism spectrum disorders comprise a vast and heterogeneous collection of neurodevelopmental problems. For the majority of these disorders, there is no single genetic cause but instead a large number of risk factors associated with the likelihood of developing symptoms. A primary goal of autism researchers is to determine whether there is some common mechanism that can explain the emergence of the various behavioral and cognitive impairments. One possible mechanism is epigenetic DNA modification, a process that changes gene expression without altering the underlying DNA sequence. Importantly, this can occur in adult brain cells and can be ‘activity-dependent,’ that is, triggered by brain activity in response to experience. Such neural responses to changes in the environment are an essential component of adaptive brain function. Therefore, dysregulation of this capacity could lead to maladaptive behavior. Hongjun Song and his colleagues at Johns Hopkins University in Baltimore propose to investigate the function of GADD45, a gene that has been implicated in activity-dependent epigenetic DNA modification and is abnormally expressed in some individuals with autism. To evaluate the gene’s role in autism, the researchers are planning a series of experiments using mice in which components of the GADD45 DNA modification pathway have been genetically altered. They plan to evaluate both gene expression and behavior in these mice. In addition, Song’s team plans to examine GADD45-associated gene expression and DNA modification in postmortem tissue from individuals with autism. Their experiments may provide new insight into the role of activity-dependent DNA modification in individuals with the disorder.