Pedunculopontine Nucleus: Functional Organization and Clinical Implications

The pedunculopontine tegmental nucleus (PPN) is a neurochemically and functionally heterogeneous structure that occupies a strategic position in the dorsal tegmentum of the midbrain and upper pons. The PPN contains cholinergic, γ-aminobutyric acid (GABA)ergic, and glutamatergic neurons; it receives direct input from the cerebral cortex, is reciprocally connected with the basal ganglia, and provides inputs to the thalamus and motor areas of the brainstem and spinal cord. Via these connections, the PPN is involved in mechanisms of cortical arousal and behavioral state control and participates in control of locomotion and muscle tone. The PPN is affected in Parkinson disease (PD) and atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Involvement of the PPN may have an important role in gait impairment in these disorders. The development of PPN deep brain stimulation (DBS) for treatment of this disabling symptom has also provided some insight into the function of the PPN in humans. There have been several recent reviews on the PPN focused on its neurochemical organization and connectivity, physiology, involvement in parkinsonian syndromes, and as a target for DBS.(1-12.)