Fig. 1

Neural pathways implicated in repetitive behaviors. a Schematic drawings of the cortico-basal ganglia-thalamic pathways including the direct and indirect pathways. The direct pathway is represented by brown color, while the indirect pathway is represented by blue color. The regions that are common in both pathways are represented with mixed brown and blue colors. Dopaminergic sources from substantia nigra pars compacta (SNc), which activate and inactivate direct and indirect pathways, respectively, are represented by green color. The projections from cortex activate both D1R and D2R-expressing GABAergic neurons in the striatum. Then, the D1R-expressing GABAergic neurons in the direct pathway inhibit the internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr). Sequentially, the GABAergic output from GPi and SNr inhibits thalamus and in turn thalamus activates the motor cortex. Thus, the final consequence of the direct pathway is activation of movements. In contrast, D2R-expressing neurons in the indirect pathway inhibit the external globus pallidus (GPe) and GPe inhibits subthalamic nucleus (STN). The STN then activates GPi and SNr, which inhibits thalamus. Hence, the final consequence of indirect pathway is inactivation of movements. b Possible neuronal mechanisms of pharmacological rescue of repetitive behaviors. mGluR5 antagonism can inhibit the direct pathway by inhibiting the D1R signaling. GABA agonists can ameliorate elevated E/I balance in the motor cortex of some ASD mouse models, and D2R antagonism may potentiate the GABAergic function in cortical areas