Heterozygous mutation of CHD8 is strongly associated with autism and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. In the current project, Albert Basson and Laura Andreae plan to study excitatory and inhibitory synaptic transmission in the prefrontal cortex of Chd8 haploinsufficient mice. Findings from these studies are expected to shed light on how Chd8 mutations disrupt autism-relevant circuits in the developing cortex.

ASD is believed to modify the balance of excitation and inhibition in brain circuits and is frequently accompanied by seizures, but precisely how and why this occurs is poorly understood. In this project, Sacha Nelson and colleagues plan to use an in vitro slice culture platform in combination with calcium imaging techniques to record activity from brain regions important for sensation and memory in four established genetic mouse models of ASD. By studying changes in neuronal and epileptiform activity over development, the progression of brain pathology and the mechanisms that normally compensate for it will be better understood.

Gastrointestinal issues are a comorbidity of ASD and individuals with mutations in CHD8 often display such symptoms. In the current project, Evan Elliott and colleagues plan to study Chd8 heterozygous mice to explore the role of Chd8 on gut epithelial cell function. Findings from this study are expected to lead to a better understanding of the relationship between Chd8 haploinsufficiency, gastrointestinal issues and behavioral phenotypes relevant to ASD.