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The physiology of the pedunculopontine nucleus: implications for deep brain stimulation

  • Neurology and Preclinical Neurological Studies - Review article
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Abstract

This brief review resolves a number of persistent conflicts regarding the location and characteristics of the mesencephalic locomotor region, which has in the past been described as not locomotion-specific and is more likely the pedunculopontine nucleus (PPN). The parameters of stimulation used to elicit changes in posture and locomotion we now know are ideally suited to match the intrinsic membrane properties of PPN neurons. The physiology of these cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for the treatment of gait and postural deficits in Parkinson’s disease (PD). The discussion explains many of the effects reported following deep brain stimulation (DBS) of the PPN by different groups and provides guidelines for the determination of long-term assessment and effects of PPN DBS. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from DBS for movement disorders. Despite these improvements, there remains a great opportunity for further understanding of the mechanisms through which DBS has its effects and for further development of appropriate technology to effect these treatments. We review the scientific basis for one of the newest targets, the PPN, in the treatment of PD and other movement disorders, and address the needs for further investigation.

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Acknowledgments

This work was supported by NIH award R01 NS020246, and by core facilities of the Center for Translational Neuroscience supported by NIH awards P20 GM103425 and P30 GM110702 to Dr. Garcia-Rill. In addition, this work was supported by grants from FONCYT-Agencia Nacional de Promoción Científica y Tecnológica; BID 1728 OC.AR.PICT-2012-1769 (to Dr. Urbano).

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The authors declare no conflict of interest.

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Correspondence to E. Garcia-Rill.

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Nomenclature of the PPN has always been inconsistent. When we began work in the region in 1979, some atlases used the contraction “PPT”, others “PPTg”, and others “PPN”, for nucleus tegmenti pedunculopontinus. We chose the “PPN” contraction for this terminology because the term “tegmental” is superfluous. The main descriptor, “pedunculo-pontine”, pinpoints the location to the body (tegmentum) of the pons near the peduncle, making the term “tegmental” unnecessary. In addition, some workers use the contraction “T” for tegmental, while others use “Tg”, adding to the variability in this term. Since there is no other “pedunculopontine” nucleus in the brain, again, we consider the term “tegmental” unnecessary. For example, the “laterodorsal tegmental nucleus” does require the “tegmental” since there is a laterodorsal “thalamic” nucleus. Most investigators contract the laterodorsal tegmental nucleus to “LDT”, but never “LDTg”. The inconsistencies remain.

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Garcia-Rill, E., Hyde, J., Kezunovic, N. et al. The physiology of the pedunculopontine nucleus: implications for deep brain stimulation. J Neural Transm 122, 225–235 (2015). https://doi.org/10.1007/s00702-014-1243-x

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