The pedunculopontine nucleus: Its role in the genesis of movement disorders

The pedunculopontine nucleus (PPN) is located in the dorso-lateral part of the ponto-mesencephalic tegmentum. The PPN is composed of two groups of neu rons: one containing acetylcholine, and the other containing non-cholinergi c neurotransmitters (GABA, glutamate). The PPN is connected reciprocally wi th the limbic system, the basal ganglia nuclei (globus pallidus, substantia nigra, subthalamic nucleus), and the brainstem reticular formation. The ca udally directed corticolimlic-ventral striatal-ventral pallidal-PPN-pontome dullary reticular nuclei-spinal cord pathway seems to be involved in the in itiation, acceleration, deceleration, and termination of locomotion. This p athway is under the control of the deep cerebellar and basal ganglia nuclei at the level of the PPN, particularly via potent inputs from the medial gl obus pallidus, substantia nigra pars reticulata and subthalamic nucleus. Th e PPN sends profuse ascending cholinergic efferent fibers to almost all the thalamic nuclei, to mediate phasic events in rapid-eye-movement sleep. Exp erimental evidence suggests that the PPN, along with other brain stem nucle i, is also involved in anti-nociception and startle reactions. In idiopathi c Parkinson's disease (IPD) and parkinson plus syndrome, overactive pallida l and nigral inhibitory inputs to the PPN may cause sequential occurrences of PPN hypofunction, decreased excitatory PPN input to the substantia nigra , and aggravation of striatal dopamine deficiency. In addition, neuronal lo ss in the PPN itself may cause dopamine-resistant parkinsonian deficits, in cluding gait disorders, postural instability and sleep disturbances. In pat ients with IPD, such deficits may improve after posteroventral pallidotomy, but not after thalamotomy. One of the possible explanations for such diffe rences is that dopamine-resistant parkinsonian deficits are mediated to the PPN by the descending pallido-PPN inhibitory fibers, which leave the palli do-thalamic pathways before they reach the thalamic targets.