Figure 2.

The models of basal ganglia in normal condition, Parkinson's disease and Parkinson's disease with levodopa-induced dyskinesia. (a) The model of basal ganglia in normal condition. Normal dopaminergic input from substantia nigra pars compacta (SNc) influences the motor movement through dopaminergic receptors D1 (direct pathway) and D2 (indirect pathway). Basically, dopaminergic stimulation on D1 receptor facilitates motor movement while stimulation on D2 receptor inhibits motor movement. In addition, hyperdirect pathway may also inhibit motor movement. (b) In Parkinson's disease (PD), loss of dopaminergic input from SNc leads to underactivity of the direct pathway and overactivity of the indirect pathway. Finally, the glutamatergic output from thalamus is reduced and decreases the motor movement. In addition, the role of hyper-direct pathway in PD is still unknown; however, the hyperdirect pathway might increase its activity in PD. (c) After long-term administration of levodopa concomitant with more degree of loss of striatal dopamine, the interconnections within nigrostriatal circuit change in the opposite directions, overactivity of the direct pathway, and underactivity of the indirect pathway produces an excessive motor movement named “levodopa-induced dyskinesia.” In addition, the role of hyperdirect pathway in PD with LID is not exactly known; however, the hyperdirect pathway might decrease the activity in PD with LID stage. PD = Parkinson's disease; LID = levodopa-induced dyskinesia; GPe = Globus pallidus externa; GPi = Globus pallidus interna; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; STN = Subthalamic nucleus; Green arrow = excitatory output; Red arrow with dashed line = inhibitory output