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Biomedical Reviews

Pedunculopontine tegmental nucleus. Part I: cytoarchitecture, transmitters, development and connections

Kamen G. Usunoff, Dimitar E. Itzev, Stephan R. Lolov, Andreas Wree


The present review compiles data on the cytoarchitecture, transmitters, development, afferent and efferent connections of the pedunculopontine tegmental nucleus (PPN). PPN is a reticular formation nucleus, located in the pontomesencephalic tegmentum, closely associated with the ascending limb of the superior cerebellar peduncle. Its most typical cells are cholinergic and comprise the Ch5 neuronal group of Mesulam. It contains also glutamatergic neurons that may contain glutamate as a sole transmitter or as a co-transmitter of acetylcholine. The cholinergic neurons use also the gaseous transmitter nitric oxide, being the most prominent nitrergic neurons in the central nervous system (CNS). In aged animals, there is practically no cell loss but there are certain drastic changes in the somatodendritic morphology. PPN has an extremely rich afferent input. All basal ganglia send axons to PPN, the strongest connection being from the substantia nigra (SN), followed by pathways arising from the subthalamic nucleus (STN) and from both pallidal segments (PAL). PPN receives afferents also from the cerebral cortex, from areas of the limbic system and hypothalamus, from the cerebellum, from the brainstem - particularly serotoninergic axons from the raphe nuclei and noradrenergic axons from the locus ceruleus - as well as from the spinal cord. The efferent connections of PPN are extremely diverse, and some of them are carried out by axons that emit divergent collaterals to two different structures. The heaviest efferent pathway of PPN is destined to the thalamus, innervating virtually all thalamic nuclei, and especially the "nonspecific" intralaminar nuclei, that innervate broad ares of the cerebral cortex. All basal ganglia are innervated and in most cases the connection is bilateral. The most significant pathway innervates the dopaminergic neurons of SN, followed by a connection to STN and PAL. Other PPN efferent connections reach the cerebellum, the superior colliculus, nuclei of cranial nerves, the reticular formation, and the spinal cord. The reviewed connections of PPN suggest that it is involved significantly in the arousal systems, and is implicated in the disturbances of sleep and wakefulness. PPN is also involved in the motor functions of CNS, as well as in the movement disorders.

Biomedical Reviews 2003; 14: 95-120.

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About The Authors

Kamen G. Usunoff
Medical University of Sofia

Dimitar E. Itzev
Bulgarian Academy of Sciences

Stephan R. Lolov
Bulgarian Academy of Sciences

Andreas Wree
University of Rostock

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