Parkinson's Disease: What role do pedunculopontine nucleus cholinergic neurons play?

Abstract

5 ISSN 1479-6708 10.2217/FNL.13.61 © 2014 Future Medicine Ltd Future Neurol. (2014) 9(1), 5–8 There is increasing evidence that cholinergic system dysfunction contributes significantly to both nonmotor and motor morbidities in Parkinson’s disease (PD) [1]. Important brain cholinergic projection systems include the well-characterized basal forebrain cortico petal system and cholinergic neurons within the pedunculopontine–lateral dorsal tegmental complex. Located at the mesopontine border, the pedunculopontine nucleus (PPN) is a phylogenetically ancient structure composed of a number of different neuronal populations [2]. Cholinergic projection neurons are prominent PPN components with strong inter connections with the basal ganglia and thalamus, and substantial descending projections to important medullary motor centers. The PPN is a key node in the regulation of both consciousness and motor function. The midbrain locomotor region, a physiologically defined region crucial for normal gait and posture, encompasses the PPN [3]. PET ligands targeting markers of cholinergic terminals enable in vivo assessment of the integrity of cholinergic projections. Combined with post-mortem studies and experimental animal work, a much clearer picture of the nature of cholinergic projection system changes and their clinical correlates is now emerging. Nonmotor symptoms such as rapid eye movement sleep behavior disorder (RBD) and possibly visual hallucinations may ref lect degeneration of PPN cholinergic neurons and their thalamic afferents in PD. Degeneration of basal forebrain cholinergic neurons and their centripetal cortical projections is a determinant of cognitive decline in PD and Alzheimer’s disease (AD) [1]. A major distinction in cholinergic systems degeneration between PD and AD is that PPN neurons and their thalamic projections degenerate in PD but remain relatively spared in AD [4]. RBD is a parasomnia that has been linked almost exclusively to a-synucleinopathies [5]. We showed recently that PD subjects reporting symptoms of RBD had evidence of more prominent cholinergic terminal loss, including within the thalamus, reflecting impaired integrity of PPN–thalamic