Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain

Samuel W. Hulbert, Yong-hui Jiang

Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.