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The pedunculopontine nucleus: From posture and locomotion to neuroepigenetics

  • Received: 21 August 2019 Accepted: 19 September 2019 Published: 30 September 2019
  • In this review, we discuss first an example of one of the symptoms of PD, freezing of gait (FOG), then we will turn to the use of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) to treat PD, and the original studies that led to identification of the PPN as one source of locomotor control and why stimulation frequency is critical, and then describe the intrinsic properties of PPN neurons that require beta/gamma stimulation in order to fully activate all types of PPN neurons. Finally, we will describe recent findings on the proteomic and molecular consequences of gamma band activity in PPN neurons, with emphasis on the potential neuroepigenetic sequelae. These considerations will provide essential information for the appropriate refining and testing of PPN DBS as a potential therapy for PD, as well as alternative options.

    Citation: T. Virmani, F. J. Urbano, V. Bisagno, E. Garcia-Rill. The pedunculopontine nucleus: From posture and locomotion to neuroepigenetics[J]. AIMS Neuroscience, 2019, 6(4): 219-230. doi: 10.3934/Neuroscience.2019.4.219

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  • In this review, we discuss first an example of one of the symptoms of PD, freezing of gait (FOG), then we will turn to the use of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) to treat PD, and the original studies that led to identification of the PPN as one source of locomotor control and why stimulation frequency is critical, and then describe the intrinsic properties of PPN neurons that require beta/gamma stimulation in order to fully activate all types of PPN neurons. Finally, we will describe recent findings on the proteomic and molecular consequences of gamma band activity in PPN neurons, with emphasis on the potential neuroepigenetic sequelae. These considerations will provide essential information for the appropriate refining and testing of PPN DBS as a potential therapy for PD, as well as alternative options.


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    Abbreviation CaMKII: calcium calmodulin kinase II; cAMP/PK: cyclic adenosine monophosphate/protein kinase; DBS: deep brain stimulation; FOG: freezing of gait; PD: Parkinson's disease; PPN: pedunculopontine nucleus; RAS: reticular activating system; REM: rapid eye movement;
    Acknowledgments



    Supported by NIH award P30 GM110702 from the IDeA program at NIGMS to the CTN. This work was also supported by the University of Arkansas Clinician Scientist Program award (to Dr. Virmani). In addition, this work was supported by grants from FONCYT-Agencia Nacional de Promoción Científica y Tecnológica; Préstamo BID 1728 OC.AR. PICT-2016-1728 (to Dr. Urbano); FONCYT-Agencia Nacional de Promoción Científica y Tecnológica; Préstamo BID 1728 OC.AR. PICT 2015-2594 (to Dr. Bisagno).

    Conflict of interest



    The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.
    All of the published studies referred to from our labs secured UAMS institutional review board (IRB) permission for human studies or institutional animal care (IACUC) approval for all animal studies prior to the performance of experiments.
    None of the published studies referred to from our labs required public registration.
    The authors declare no conflict of interest.

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