Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic nucleus and substantia nigra pars reticulata in a 6‐hydroxydopamine rat model
- 24 October 2006
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 24 (8), 2275-2282
- https://doi.org/10.1111/j.1460-9568.2006.05106.x
Abstract
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.Keywords
This publication has 59 references indexed in Scilit:
- Unilateral lesion of the pedunculopontine nucleus induces hyperactivity in the subthalamic nucleus and substantia nigra in the ratEuropean Journal of Neuroscience, 2005
- On the Relationships Between the Striatum and the Pedunculopontine Tegmental NucleusCritical Reviews™ in Neurobiology, 1997
- Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates:Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistryJournal of Comparative Neurology, 1996
- Cholinergic, GABAergic, and glutamate-enriched inputs from the mesopontine tegmentum to the subthalamic nucleus in the ratJournal of Neuroscience, 1995
- The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonismJournal of Neurophysiology, 1994
- Reversal of Rigidity and Improvement in Motor Performance by Subthalamic High‐frequency Stimulation in MPTP‐treated MonkeysEuropean Journal of Neuroscience, 1993
- Reversal of Experimental Parkinsonism by Lesions of the Subthalamic NucleusScience, 1990
- Primate models of movement disorders of basal ganglia originTrends in Neurosciences, 1990
- Functional architecture of basal ganglia circuits: neural substrates of parallel processingTrends in Neurosciences, 1990
- The functional anatomy of basal ganglia disordersTrends in Neurosciences, 1989