Behavioral and Anatomical Cerebellar Deficits in Mouse Models of Autism Spectrum Disorders

Abstract

With as many as 1 in 68 children afflicted, autism spectrum disorders (ASDs) impact a significant portion of the population. ASDs comprise a group of heterogeneous conditions—including autistic disorder and Rett syndrome—and are typically characterized by moderate to severe impairments in social, communicative, and behavioral functions. A number of susceptibility genes and anatomical abnormalities in the brain are associated with ASD pathogenesis in humans. Cerebellar abnormalities in particular have been found in ASD patients. The objective of this study was to use genetic mouse models of ASDs to uncover behavioral and anatomical cerebellar deficits associated with each ASD-related mutation in SHANK3, CNTNAP2, MECP2, and human chromosome 15q11-13. Delay eyeblink conditioning was used as a behavioral indicator of cerebellar function in mutant mice, with results showing an association between various problems in cerebellar-dependent learning and the genetic mutation. Subsequent histological experiments on cerebellar tissue examined the anatomical correlates behind the behavioral cerebellar deficits seen in mutant mice during eyeblink conditioning. Overall, the findings indicated that cerebellar deficits in Shank3, Cntnap2, Mecp2, and 15q11-13 mouse models manifested both behaviorally and anatomically in ways specific to each mutation. This study therefore bridged an important gap between genetics and cerebellar neurobiology in ASDs, increasing our understanding of ASD development and offering new insight into future screening and treatment strategies.