The regulation of expression of some autism candidate genes by neuronal membrane depolarization suggests the appealing hypothesis that neural activity–dependent regulation of synapse development may be a mechanism common to several autism mutations. Early brain development is driven largely by intrinsic patterns of gene expression that do not depend on experience-driven synaptic activity (44). Mutations in the genes active in early development can lead to brain malformations or severe mental retardation. In contrast, postnatal brain development requires input from the environment that triggers the release of neurotransmitter and promotes critical aspects of synaptic maturation. During this process, neural activity alters the expression of hundreds of genes, each with a defined temporal course that may be particularly vulnerable to gene dosage changes. The connection between experience-dependent neural activity and gene expression in the postnatal period forms the basis of learning and memory, and autism symptoms typically emerge during these later stages of development. Our finding that deletions of genes regulated by neuronal activity or regions potentially involved in regulation of gene expression in autism suggests that defects in activity-dependent gene expression
