Aberrations of the brain’s myelinated white matter have come to light in autism spectrum disorders (ASDs). Neuroligin 3, an ASD risk gene, is strongly expressed in myelin-forming glial cells. Michelle Monje proposes to assess myelination and myelin plasticity in a neuroligin 3 mutant mouse model to understand how changes in myelin may be involved in the pathophysiology of ASD.

Anis Contractor will assess how the development of synapses and circuits in the striatum are disrupted in a novel mouse model of autism that harbors a gain-of-function mutation in the voltage-gated calcium channel Cav1.3 in order to gain an understanding of how this mutation contributes to autism risk.

Using identical visual stimulation protocols in mice and children — both typically developing and those possessing homologous ASD-associated genetic mutations — Mark Bear and Charles Nelson aim to identify behavioral and neurophysiological biomarkers that could accelerate diagnosis and elucidate new therapeutic targets for ASD.

Jess Cardin and Michael J. Higley will establish a functional screen (using a CRISPR/Cas9-induced gene disruption system and multiscale in vivo calcium imaging in awake mice) for the assessment of common cellular- and circuit-level cortical dysregulation phenotypes associated with mutations in ASD risk genes.

Hisashi Umemori will use knockout mouse models to identify the roles played by a group of ASD-linked protocadherins in regulating specific cortico-striatal circuits, aiming to reveal novel molecular and circuit mechanisms underlying the pathophysiology of ASD.

Yoram Bonneh will investigate basic cognitive skills related to receptive language and reading in minimally verbal individuals with autism spectrum disorder via the analysis of involuntary eye movements in response to pictures, text and sound. These studies are intended to test the hypothesis that core action-control deficits for voluntary or intentional behavior may result in a significant gap between the observed and actual cognitive abilities in such individuals.

Using new magnetic resonance imaging techniques and analysis approaches to identify focal cortical dysplasias (FCDs), Ruth Carper aims to determine whether FCDs occur more frequently in individuals with ASDs than is currently appreciated and to understand what effects FCDs have on cognition and behavior in ASD.

Geoffrey Goodhill will address how the early development of neural sensory circuits is altered in autism spectrum disorders, using a zebrafish model of fragile X syndrome to examine alterations in the developmental patterns of neural activity and their relationship to changes in visually driven behaviors.