Delay and Trace Eyeblink Conditioning in Mouse Models of Autism Spectrum Disorder: An Analysis of Cerebellar and Hippocampal Function

Abstract

Autism Spectrum Disorder (ASD) is a pervasive, genetically-based disorder that has seen drastic increases in prevalence over the past several decades. Despite much research attention, neurobiological markers for the disorder are lacking. Furthermore, the role of specific genes in development of ASD is elusive because the disorder is incredibly genetically heterogeneous. This study presents an investigation of the neurobiological effects of mutations in Cntnap2 and Shank3 in mouse models of non-syndromic ASD. Delay eyeblink conditioning, which probes cerebellar function, was conducted in these two mouse models. Additionally, a pilot study of trace eyeblink conditioning, which reflects hippocampal function, was conducted in the models to provide preliminary data. Delay eyeblink conditioning results show a significant effect of both Cntnap2 and Shank3 mutations on cerebellar function, specifically in the cerebellar cortex and deep nuclei. Pilot data from trace eyeblink conditioning suggest that the mutations may have an effect on hippocampal function as well, although follow-up studies are needed. These findings can have substantial implications for understanding ASD. Furthermore, the results may have an impact on future screening, treatment, and resource allocation for the disorder on a global level.