Renata Batista-Brito will use optical tools, electrophysiology and behavioral assessments in an Mef2C knockout mouse model of autism to determine the developmental role of GABAergic dysfunction in regulating sensory processing of cortical networks and behavior.
Hirofumi Morishita plans to identify common corticothalamic circuitry deficits in genetic mouse models of autism that affect social behaviors and establish preclinical strategies for ameliorating these social deficits.
Sensory hypersensitivity is a central issue in autism and autism-related disorders like fragile X syndrome but relatively little is known about the underlying brain mechanisms. In this project, Richard Salvi plans to combine the use of novel behavioral assays for assessing sound hypersensitivity in rats with state-of-the-art electrophysiological and analytical techniques to determine the nature of auditory perceptual and circuit abnormalities in a rat model of fragile X syndrome.
Noninvasive neuroimaging, such as fMRI, has provided insights into dysfunction of large-scale neural systems in ASD and its relationship to cognitive deficits, yet it is unclear how such biomarkers relate to cellular and synaptic features of human brains. To help bridge this gap, John Murray and Alan Anticevic will utilize existing ASD neuroimaging data sets to provide insight about: (i) cortical circuit alterations in a mechanistic computational model, (ii) brain-behavior relationships across individuals and (iii) brain-wide patterns of gene expression in ASD.
Jun Hee Kim will investigate how Scn2a expression in oligodendrocytes contributes to myelination and neural connectivity during brain development in mice and determine whether loss of oligodendroglial Scn2a impacts social and cognitive behaviors relevant to autism. Understanding how deficits in Nav1.2-mediated oligodendroglial excitability and adaptive myelination could contribute to autism may generate new potential therapeutic strategies for treating this disorder.
Linda Wilbrecht proposes that an inability to appropriately update behavior based on probabilistic feedback represents a core learning deficit in ASD and that specific frontal-striatal circuits may contribute to these deficits. She will test these ideas in two genetic mouse models of ASD to help determine if ASD risk genes affect specific forms of learning and/or specific cell types more than others.