Most of the genes known to be associated with autism seem to regulate how neurons communicate with each other at structures called synapses. Li-Huei Tsai and her colleagues at the Massachusetts Institute of Technology study the role of CDK5, an enzyme involved in synapse activity, and its influence on SHANK3, another protein known to be important in autism.

The neurobiology behind the classic signs of autism — repetitive behaviors, impaired social interactions and language deficits — is largely unknown. Based on their studies on a mouse model of obsessive-compulsive disorder, Guoping Feng and his colleagues at Duke University propose that an imbalance between two circuits of neurons may underlie the repetitive behaviors associated with autism.

Roughly one percent of cases of autism are associated with deletions within a single region of chromosome 16, which contains nearly 30 genes. It is unclear which, and how many, of these genes are crucial in this association. Hazel Sive at the Whitehead Institute of Biomedical Research and her colleagues plan to determine which of these genes regulate brain development in zebrafish, in order to identify the genes that may contribute to the development of autism spectrum disorders.

The study of autism is best approached using a variety of disciplines, a practice greatly facilitated by the large amount of data shared among collaborators in the Simons Simplex Collection. Steve Petersen and his colleagues at Washington University in St. Louis plan to contribute new brain imaging data to the mix using a recently developed tool called resting-state functional connectivity MRI (fcMRI).

Autism arises in early childhood, during a period of intense learning when many of the brain’s connections are modified by experience. Eric Kandel, Yun-Beom Choi and Craig Bailey of Columbia University are using animal models of memory formation to investigate how two autism-associated proteins — neuroligin and neurexin — regulate this process.

The heritable nature of autism has been borne out by research showing that identical twins and siblings of children with autism are at a greater risk of the disorder than children in the general population. Zachary Warren and his colleagues at the Vanderbilt Kennedy Center plan to follow 66 such school-aged siblings to gauge cognitive, language and behavioral outcomes.

Like autism, Rett syndrome arises in young children with a progressive loss of skills such as speech and control of movements, and is frequently accompanied by mental retardation and seizures. Mutations in the gene MECP2 are known to cause Rett syndrome. Josh Huang and his colleagues at Cold Spring Harbor Laboratory plan to study how the MECP2 gene regulates brain circuitry — information that may have implications for both Rett syndrome and autism.

Autism arises from mutations in the genome, but several studies have shown that many of these mutations occur de novo — that is, they are non-inherited mutations introduced during the parents’ gamete production. Jay Gingrich at the New York State Psychiatric Institute and his colleagues plan to study a mouse model of autism to investigate whether advanced paternal age is linked to a higher frequency of genomic aberrations.

Genetic studies have linked several new genes to increased risk of autism. The challenge, however, is in understanding how mutations in these genes disrupt neural development and cause the disorder. Ted Dawson and his colleagues at Johns Hopkins University plan to undertake this task for the signaling protein known as the MET receptor.