Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model
The pedunculopontine nucleus (PPN) and the subthalamic nucleus (STN) are reciprocally connected by excitatory projections. In the 6-hydroxydopamine (6-OHDA) rat model the PPN was found to be hyperactive. Similarly, the STN and the substantia nigra pars reticulata (SNr) showed increased activity in Parkinson's disease (PD) animal models. A lesion of the STN was shown to restore increased activity levels in the SNr of 6-OHDA-treated rats. As the STN and the PPN were reciprocally connected by excitatory projections and both structures were shown to be hyperactive in PD animal models, the present study was performed in order to investigate the changes in neuronal activity of the STN and SNr under urethane anesthesia after unilateral ibotenic acid lesioning of the PPN in animals with previous unilateral 6-OHDA lesions of the substantia nigra pars compacta (SNc). The firing rate of STN neurons significantly increased from 10.3 +/- 0.6 spikes/s (mean +/- SEM) to 17.8 +/- 1.8 spikes/s after SNc lesion and returned to normal levels of 10.8 +/- 0.7 spikes/s after additional lesion of the PPN. Similarly, the firing rate of SNr neurons significantly increased from 19.0 +/- 1.1 to 25.9 +/- 1.4 spikes/s after SNc lesion, the hyperactivity being reversed after additional PPN lesion to 16.8 +/- 1.2 spikes/s. The reversal of STN and SNr hyperactivity of 6-OHDA-treated rats by additional PPN lesion suggests an important modulatory influence of the PPN on STN activity. Moreover, these findings could indicate a new therapeutic strategy in PD by interventional modulation of the PPN.
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Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Exercise Hlth & Technol Ctr, Dept Phys Educ, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
Lin, Muxin
Wang, Ying
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Southern Univ Sci & Technol, Core Res Facil, Shenzhen, Peoples R ChinaShanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
Wang, Ying
Wang, Yi
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Enlight Med Technol Shanghai Co Ltd, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
Wang, Yi
Chen, Fujun
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Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
Shanghai Jiao Tong Univ, Exercise Hlth & Technol Ctr, Dept Phys Educ, Shanghai, Peoples R China
World Laureates Assoc, WLA Labs, Shanghai, Peoples R ChinaShanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China
机构:
Univ Toronto, Inst Biomed Engn, Toronto, ON, Canada
Univ Toronto, Max Planck Ctr Neural Sci & Technol, Toronto, ON, Canada
Univ Hlth Network, Krembil Brain Inst, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Leavitt, Dallas
Alanazi, Frhan I.
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Physiol, Toronto, ON, Canada
King Saud Univ, Prince Sultan bin Abdulaziz Coll Emergency Med Ser, Dept Basic Sci, Riyadh, Saudi ArabiaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Alanazi, Frhan I.
Al-Ozzi, Tameem M.
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Physiol, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Al-Ozzi, Tameem M.
Cohn, Melanie
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Cohn, Melanie
Hodaie, Mojgan
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Surg, Toronto, ON, Canada
Univ Hlth Network, Toronto Western Hosp, Div Neurosurg, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Hodaie, Mojgan
Kalia, Suneil K.
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Surg, Toronto, ON, Canada
Univ Hlth Network, Toronto Western Hosp, Div Neurosurg, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Kalia, Suneil K.
Lozano, Andres M.
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Surg, Toronto, ON, Canada
Univ Hlth Network, Toronto Western Hosp, Div Neurosurg, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
Lozano, Andres M.
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Milosevic, Luka
Hutchison, William D.
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Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada
Univ Toronto, Dept Physiol, Toronto, ON, Canada
Univ Toronto, Dept Surg, Toronto, ON, Canada
Univ Hlth Network, Toronto Western Hosp, Div Neurosurg, Toronto, ON, CanadaUniv Toronto, Inst Biomed Engn, Toronto, ON, Canada
机构:
Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA
Penn State Univ, Dept Elect Engn, University Pk, PA 16802 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Gilmour, Timothy P.
Piallat, Brigitte
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INSERM, Grenoble Inst Neurosci, Grenoble, FrancePenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Piallat, Brigitte
Lieu, Christopher A.
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Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Lieu, Christopher A.
Venkiteswaran, Kala
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Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Venkiteswaran, Kala
Ramachandra, Renuka
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AT Still Univ, Kirksville Coll Med, Kirksville, MO 63501 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Ramachandra, Renuka
Rao, Anand N.
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Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Rao, Anand N.
Petticoffer, Andrew C.
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Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Petticoffer, Andrew C.
Berk, Matthew A.
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Albany Med Coll, Albany, NY 12208 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Berk, Matthew A.
Subramanian, Thyagarajan
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Penn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA
Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USAPenn State Univ, Coll Med, Dept Neurol, Hershey, PA 17033 USA