Differential Consequences of Habitual Responding in a Mouse Model of Repetitive Behavior

Restricted, repetitive behavior (RRB) is diagnostic for autism spectrum disorder (ASD) and characteristic of a number of neurodevelopmental, psychiatric, and neurological disorders. RRB seen in ASD includes repetitive motor behavior and behaviors reflecting resistance to change and insistence on sameness. C58 mice provide a robust model of repetitive motor behavior and have shown resistance to change in a reversal learning task. We further characterized resistance to change in this model by inducing habitual responding and testing for differences in the ability to suppress habitual behavior and shift to goaldirected responding. We found no differences between C58 and control (C57BL/6) mice in the acquisition of operant tasks, habit formation, and expression of habitual responding. Habitual responding, however, induced significant reversal learning and contingency reversal performance deficits in C58 mice compared with C57BI/6 mice. Decreased dendritic spine density of the dorsomedial striatum in C58 mice was related to higher repetitive motor behavior, whereas dendritic spine density in the subthalamic nucleus was significantly positively correlated with improved contingency reversal performance in both C58 and C57BL/6 mice. Our results demonstrate that induction of habitual responding markedly impaired the ability of C58 mice to shift to goal-directed behavior. Such impairment may have resulted from the effects of the induction of habitual responding on already compromised basal ganglia circuitry mediating repetitive motor behavior. These findings provide additional evidence for the translational value of the C58 model in modeling RRB in neurodevelopmental disorders.