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Systems Biology of Autism: The Case for the Cerebellum

A great deal of research into the biological basis of autism spectrum disorders has revealed that impairment of basic processes at the synaptic level may be the deepest cause of this neurodevelopmental disorder. Many of the proteins implicated by genetics studies are found at the synapse and have well-established roles in mediating synaptic plasticity. A hard problem for neuroscientists is to explain how faulty processes at the synapse can account for the social and communication difficulties experienced by persons with autism. Clearly, therapeutic breakthroughs for autism would be forthcoming if a specific neuronal cell type in a specific neurological circuit were shown to be the primary site of atypical plasticity, analogous to the discovery that weakened dopamine-producing cells in the substantia nigra can result in Parkinson’s Disease. There have been suggestions over the years that Purkinje cells, the primary integrators, comparators, and output cells of the olivocerebellar circuit might function differently in autism. The purpose of this meeting was to explore the idea that damage to the cerebellum during development, or ongoing errors in synaptic regulation, might explain the social and communication deficits seen in autism.

Matthew P. Anderson, M.D. Ph.D., Harvard Medical School, Beth Israel Deaconess Medical Center

Ray Kelleher, MD, Ph.D., Harvard Medical School, Massachusetts General Hospital

Tal Kenet, Ph.D., Harvard Medical School, Massachusetts General Hospital

Determining how Purkinje-cell-specific manipulations lead to behavioral deficits consistent with autism
Wade Regehr, Ph.D., Harvard Medical School

Autistic-like behavior in Purkinje cell Tsc1 mutants
Mustafa Sahin, MD, Ph.D., Children’s Hospital Boston

Dennis P. Wall, Ph.D., Harvard Medical School

Developmental diaschisis and cerebellar contributions to autism spectrum disorder
Sam S-H Wang, Ph.D., Princeton University

Andrew W. Zimmerman, MD, Lurie Family Autism Center, Massachusetts General Hospital


The Nancy Lurie Marks Family Foundation, Wellesley, MA