Uncovering the impact of 16p11.2 deletion on neurons mediating motivated behavior

Autism spectrum disorders (ASD) are strongly sex-biased. Boys are four times more likely to receive a diagnosis than girls, with ASDs affecting an estimated 1 in 42 males in the U.S. The biological mechanisms contributing to these sex differences are currently unknown.

Using a mouse model of one of the most common genetic deletions found in individuals with ASD (the 16p11.2 region on chromosome 16), Ted Abel and his colleagues at the University of Pennsylvania have found male-specific behavioral deficits mirroring those in autism. Specifically, the researchers found that males expressing only one of the two copies of this chromosomal region exhibit deficits in motivation and reward learning. These behaviors implicate the striatum, an area of the brain that is known to be involved in reward learning and whose structure and function are affected in ASD.

The striatum is a heterogeneous brain region, consisting of different anatomical subregions and cell types. Abel and his colleagues propose to discover which regions of the striatum and which types of neurons contribute most strongly to the male-specific deficits seen in this 16p11.2 mouse model of autism. The team will use targeted behavioral, genetic, and molecular sequencing approaches to address this question. Together, these experiments will help to glean insight into the brain regions and cell types responsible for the male-specific deficits seen in ASDs.