Individuals with autism spectrum disorder experience difficulty integrating across sensory modalities, such as sight and sound. Multisensory integration is particularly prevalent in the subcortical superior colliculus, yet studies to date have not investigated its potential contributions to ASD. In this study, Feinberg plans to test the hypothesis that superior colliculus multisensory integration is altered in mouse models of ASD.

Gabel will utilize mouse models to explore how ASD-associated mutations in DNMT3A alter DNA methylation in the brain and drive ASD pathology.

Dysfunction in SCN2A, which encodes the neuronal sodium channel NaV1.2, is strongly linked to autism spectrum disorder (ASD). Building on the recent finding that multiple ASD-associated mutations in SCN2A dampen or eliminate NaV1.2 channel function, the Bender Lab is now exploring how loss of SCN2A function affects developing and mature neuronal networks in mouse models.

Blencowe will identify and characterize small molecules to rescue activity-dependent neuronal microexon splicing, providing a potential therapeutic strategy for autism.

Dysregulation of glutamatergic neurotransmission is believed to contribute to the development of autism spectrum disorder (ASD). Bruce Herring’s laboratory recently identified a hotspot of ASD-related de novo mutations in the glutamatergic synapse regulatory protein Trio. Herring’s team now aims to precisely characterize the impact these ASD-related Trio mutations have on glutamatergic synapse function and behavior.

Portera-Cailliau and O’Donnell will study neural responses to tactile stimuli in fragile X syndrome mice to test whether sensory representations are varying and unstable over time.

Meaburn and Jones will test causal paths between ASD genetic risk and disruptions in the brain systems underpinning social attention, and examine how candidate protective environmental factors might moderate genetic risk.

Tsai will delineate contributions of cerebellar dysfunction to autism-related behaviors in mice and assess benefits of cerebellar neuromodulation to treat these behaviors.

Individuals with autism frequently experience visceral pain, constipation and diarrhea, but the mechanisms underlying such gastrointestinal symptoms are poorly understood. In the current project, David Julius’ laboratory is focused on delineating the properties of enterochromaffin cells, the serotonin-producing epithelial cells of the gut that detect noxious agents, communicate with sensory nerve fibers and contribute to visceral pain

By integrating in vitro, ex vivo and in vivo techniques, Ori-McKenney will provide insight into how MNB/DYRK1a contributes to autism.