Thalamic degeneration in MPTP-treated Parkinsonian monkeys: impact upon glutamatergic innervation of striatal cholinergic interneurons
In both Parkinson’s disease (PD) patients and MPTP-treated non-human primates, there is a profound neuronal degeneration of the intralaminar centromedian/parafascicular (CM/Pf) thalamic complex. Although this thalamic pathology has long been established in PD (and other neurodegenerative disorders), the impact of CM/Pf cell loss on the integrity of the thalamo-striatal glutamatergic system and its regulatory functions upon striatal neurons remain unknown. In the striatum, cholinergic interneurons (ChIs) are important constituents of the striatal microcircuitry and represent one of the main targets of CM/Pf-striatal projections. Using light and electron microscopy approaches, we have analyzed the potential impact of CM/Pf neuronal loss on the anatomy of the synaptic connections between thalamic terminals (vGluT2-positive) and ChIs neurons in the striatum of parkinsonian monkeys treated chronically with MPTP. The following conclusions can be drawn from our observations: (1) as reported in PD patients, and in our previous monkey study, CM/Pf neurons undergo profound degeneration in monkeys chronically treated with low doses of MPTP. (2) In the caudate (head and body) nucleus of parkinsonian monkeys, there is an increased density of ChIs. (3) Despite the robust loss of CM/Pf neurons, no significant change was found in the density of thalamostriatal (vGluT2-positive) terminals, and in the prevalence of vGluT2-positive terminals in contact with ChIs in parkinsonian monkeys. These findings provide new information about the state of thalamic innervation of the striatum in parkinsonian monkeys with CM/Pf degeneration, and bring up an additional level of intricacy to the consequences of thalamic pathology upon the functional microcircuitry of the thalamostriatal system in parkinsonism. Future studies are needed to assess the importance of CM/Pf neuronal loss, and its potential consequences on the neuroplastic changes induced in the synaptic organization of the thalamostriatal system, in the development of early cognitive impairments in PD.
KeywordsParkinson’s disease Non-human primates Striatum vGluT2 Thalamostriatal Parafascicular
The authors thank Susan Jenkins for technical assistance. We also thank Dr. Kalynda Gonzales for her constructive inputs and discussions about part of the work presented in this manuscript. This work was supported by NIH Grants (R01NS083386; P50NS098685) and the NIH/ORIP P51 NIH base Grant (P51OD011132) of the Yerkes National Primate Research Center.
This study was funded by the National Institutes of Health (NIH, USA) Grants (R01NS083386; P50NS098685) and the NIH/ORIP P51 NIH base Grant (P51OD011132) of the Yerkes National Primate Research Center.
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Conflict of interest
The authors declared that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors. All procedures performed in studies involving animals were in accordance with the ethical standards. The housing, feeding, and experimental conditions used in these studies followed the guidelines by the National Institutes of Health, and are approved by Emory University’s Institutional Animal Care and Use Committee (IACUC).
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