Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability

Abstract

Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity. Treatments that target the balance between excitation and inhibition in these regions are able to reverse pathological phenotypes, elucidating this deficit as a commonality across models and opening new avenues for intervention.

Figure 1. Disrupted networks in ASD and ID mouse models

A simplified schematic depicting brain regions and circuits shown to be impaired in mice with Fmr1, Mecp2, Shank3, and Syngap1 mutations summarized in this article. The color of the dot, which corresponds to a genetic mutation, illustrates which mouse model exhibits impairments in that region. Impairments include disruption in E/I balance, hypersynchrony, and precocious synaptic maturation. Regions where pathological phenotypes have been reversed with genetic restoration, stimulation, or pharmacological treatments are in red.