Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease
The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was propos...
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doaj-f76a291bf2634d38ba2abeba715975ff2021-03-22T12:47:07ZengElsevierNeurobiology of Disease1095-953X2019-08-011284048Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson diseaseLaurent Goetz0Brigitte Piallat1Manik Bhattacharjee2Hervé Mathieu3Olivier David4Stéphan Chabardès5Grenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, France; Corresponding author at: Grenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France.Grenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, FranceGrenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, FranceGrenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, France; Unité Mixte de Service IRMaGe, Grenoble Alpes Hospital, F-38000 Grenoble, France; Unité Mixte de Service 3552, CNRS, F-38000 Grenoble, FranceGrenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, FranceGrenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France; Université Grenoble Alpes, Grenoble, France; Department of Neurosurgery, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; CEA Clinatec-Minatec, Grenoble, FranceThe pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear.Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait.http://www.sciencedirect.com/science/article/pii/S0969996118303942Pedunculopontine nucleusMicro electrode recording |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurent Goetz Brigitte Piallat Manik Bhattacharjee Hervé Mathieu Olivier David Stéphan Chabardès |
spellingShingle |
Laurent Goetz Brigitte Piallat Manik Bhattacharjee Hervé Mathieu Olivier David Stéphan Chabardès Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease Neurobiology of Disease Pedunculopontine nucleus Micro electrode recording |
author_facet |
Laurent Goetz Brigitte Piallat Manik Bhattacharjee Hervé Mathieu Olivier David Stéphan Chabardès |
author_sort |
Laurent Goetz |
title |
Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease |
title_short |
Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease |
title_full |
Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease |
title_fullStr |
Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease |
title_full_unstemmed |
Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease |
title_sort |
spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in mptp-induced primate model of parkinson disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2019-08-01 |
description |
The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear.Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait. |
topic |
Pedunculopontine nucleus Micro electrode recording |
url |
http://www.sciencedirect.com/science/article/pii/S0969996118303942 |
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