A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome

Autism is a complex neurogenetic disorder affecting one in 150 children. Little is known about the brain pathology that underlies autism spectrum disorders, however, gross brain morphology appears intact. Using functional Magnetic Resonance Imaging (fMRI) we have identified a few key brain regions that are engaged during various aspects of social communication in typical but not autistic children. These brain regions include inferior frontal cortex, amygdala, basal ganglia, and medial prefrontal cortex. In a series of studies, we demonstrate that a fundamental deficit in autism is that these brain regions are not engaged automatically when presented with relevant stimuli, but respond only to explicit direction of attention. Further, we find a general deficit in basal ganglia structures that are critical for processing rewards and for implicit or probabilistic learning. Deficits in implicit learning may lead to a wide range of deficits associated with autism including reduced response to social rewards, poor imitation, and reduced interest in social stimuli. We will also discuss possible links between autism susceptibility genes and development of these brain structures.