Animal models of restricted repetitive behavior in autism

Abstract

Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather than attempts to model the etiology or pathophysiology of restricted, repetitive behavior, as these are poorly understood. This review focuses on our work with deer mice which exhibit repetitive behaviors associated with environmental restriction. Repetitive behaviors are the most common category of abnormal behavior observed in confined animals and larger, more complex environments substantially reduce the development and expression of such behavior. Studies with this model, including environmental enrichment effects, suggest alterations in cortical-basal ganglia circuitry in the development and expression of repetitive behavior. Considerably more work needs to be done in this area, particularly in modeling the development of aberrant repetitive behavior. As mutant mouse models continue to proliferate, there should be a number of promising genetic models to pursue.

Fig. 1

Cortical-basal ganglia circuitry. Green indicates projection uses glutamate as a neurotransmitter; red indicates use of GABA; blue indicates use of dopamine. Abbreviations: GPe (external aspect of the globus pallidus); GPi (internal aspect of the globus pallidus); STN (sub-thalamic nucleus); SNpr (substantia nigra pars reticulata); SNpc (substantia nigra pars compacta). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)