The role of the pedunculopontine tegmental nucleus in experimental Parkinsonism in primates

To clarify the role of the pedunculopontine tegmental nucleus (PPN) in motor behavior, we have conducted a series of experiments in primates. In the first part, PPN was damaged locally with kainic acid, which resulted in mild hemiparkinsonism in the contralateral limbs. In the second part, muscimol (a GABA agonist) was locally injected into the PPN area in monkeys who had been trained to perform a lever-pull movement with an arm, resulting in a slowness of movement and a delay of the movement onset. In the third part, a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was systemically injected in monkeys with prior PPN lesioning. These monkeys developed no, or if any, very mild parkinsonism. PPN lesioning was supposed to have protected the nigral neurons from the MPTP- toxicity. The PPN facilitates the motor system through its nigral projection. The decreased activity of the PPN may underlie the pathophysiology of parkinsonism.