The pedunculopontine nucleus and Parkinson's disease

Akinesia and gait disturbances are particularly incapacitating for patients with Parkinson's disease. The anatomical and physiological substrates for these disturbances are poorly understood. The pedunculopontine nucleus (PPN) is thought to be involved in the initiation and modulation of gait and other stereotyped movements, because electrical stimulation and the application of neuroactive substances in the PPN can elicit locomotor activity in experimental animals, Glutamatergic neurones of the PPNd (pars dissipatus) are thought to be important regulators of the basal ganglia and spinal cord. The other component of the PPN, the cholinergic pars compacta (PPNc), is a principal component in a feedback loop from the spinal cord and limbic system back into the basal ganglia and thalamus, Electrophysiological studies suggest that 'bursting' glutamatergic PPNd neurones are related to the initiation of programmed movements while non-bursting cholinergic PPNc neurones are related to the maintenance of steady-state locomotion. Furthermore, since patients with Parkinson's disease have significant loss of PPN neurones and experimental lesions in the PPN of normal monkeys result in akinesia, the degeneration of PPN neurones or their dysfunction may be important in the pathophysiology of locomotor and postural disturbances of parkinsonism, The goal of this review is (i) to highlight the anatomical connections and physiological attributes of the PPN, (ii) to discuss how the function of these connections may be altered in the parkinsonian state, and (iii) to speculate how present and potential future therapy directed to the PPN might improve akinesia and gait difficulties in parkinsonian patients.