Complementary corticostriatal circuits orchestrate action repetition and switching

Action sequencing is fundamental to behavior. A critical decision for survival and reproduction is whether to repeat a current action or switch to a different one. However, the neural mechanisms governing action repetition and switching remain largely unknown. In mice trained to perform heterogeneous action sequences, we found that the M1-DLS circuit regulates action repetition, while the PrL-DMS pathway controls action switching. These distinct functions arise from preferential innervation of striatal D1-SPNs by M1 and D2-SPNs by PrL, respectively. In a Shank3 knockout mouse model of ASD, the D1/D2 innervation ratio in the PrL-DMS pathway was reversed, leading to impaired action switching and repetitive behaviors. Genetic restoration of Shank3 in the DMS rescued both physiological and behavioral deficits. These findings reveal how the brain orchestrates action sequencing in health and disease.