Sensory experience and learning refine circuits through elimination of excitatory synapses, a process that depends on activity-driven transcription control and that is deficient in humans with ASD and mouse ASD models. Kimberly Huber and Tae-Kyung Kim will determine the role of ASD-linked epigenetic factors in activity-driven synapse elimination using mouse model systems and identify their gene regulatory networks at the single neuron level.

Mark Blumberg will perform behavioral and neurophysiological assessments in 16p11.2 deletion mice to determine whether the early sensorimotor and sleep disturbances observed in autism have a common link.

Anna Penn will assess cerebellar white matter and circuitry alterations in a new mouse model that lacks placental expression of the neurosteroid allopregnanolone. These changes will be compared to those observed in mouse models of ASD risk genes to identify common circuits that are fundamental to the expression of behavioral deficits relevant to ASD.

Markus Meister will detect and analyze abnormal circuit functions of the retina in mouse models of autism in order to draw links between autism genes and neuronal circuit processing.

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.