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Journal of Neural Transmission

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01-10-2011 | Movement Disorders - Original Article

The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications

Arousal from slices to humans: implications for DBS

Authors: Edgar Garcia-Rill, Christen Simon, Kristen Smith, Nebosja Kezunovic, James Hyde

Published in: Journal of Neural Transmission | Issue 10/2011

Abstract

One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. The PPN is a posterior midbrain site known to induce locomotion in decerebrate animals when activated at 40–60 Hz, and has become a target for DBS in disorders involving gait deficits. We developed a research program using brainstem slices containing the PPN to study the cellular and molecular organization of this region. We showed that PPN neurons preferentially fire at gamma band frequency (30–60 Hz) when maximally activated, accounting for the effects of electrical stimulation. In addition, we developed the P13 midlatency auditory evoked potential, which is generated by PPN outputs, in freely moving rats. This allows the study of PPN cellular and molecular mechanisms in the whole animal. We also study the P50 midlatency auditory evoked potential, which is the human equivalent of the rodent P13 potential, allowing us to study PPN-related processes detected in vitro, confirmed in the whole animal, and tested in humans. Previous findings on the P50 potential in PD suggest that PPN output in this disorder is overactive. This translational research program led to the discovery of a novel mechanism of sleep–wake control based on electrical coupling, pointing the way to a number of new clinical applications in the development of novel stimulants (e.g., modafinil) and anesthetics. In addition, it provides methods for monitoring therapeutic efficacy of DBS in humans and animal models.

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Title: The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications
Arousal from slices to humans: implications for DBS
Authors: Edgar Garcia-Rill
Christen Simon
Kristen Smith
Nebosja Kezunovic
James Hyde
Publication date: 01-10-2011
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 10/2011
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-010-0500-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications

Arousal from slices to humans: implications for DBS

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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