Differential synaptic plasticity of the corticostriatal and thalamostriatal systems in an MPTP-treated monkey model of parkinsonism.

Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
European Journal of Neuroscience (Impact Factor: 3.67). 05/2008; 27(7):1647-58. DOI: 10.1111/j.1460-9568.2008.06136.x
Source: PubMed

ABSTRACT Two cardinal features of Parkinson's disease (PD) pathophysiology are a loss of glutamatergic synapses paradoxically accompanied by an increased glutamatergic transmission to the striatum. The exact substrate of this increased glutamatergic drive remains unclear. The striatum receives glutamatergic inputs from the thalamus and the cerebral cortex. Using vesicular glutamate transporters (vGluTs) 1 and 2 as markers of the corticostriatal and thalamostriatal afferents, respectively, we examined changes in the synaptology and relative prevalence of striatal glutamatergic inputs in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys using electron microscopic immunoperoxidase and confocal immunofluorescence methods. Our findings demonstrate that the prevalence of vGluT1-containing terminals is significantly increased in the striatum of MPTP-treated monkeys (51.9 +/- 3.5% to 66.5 +/- 3.4% total glutamatergic boutons), without any significant change in the pattern of synaptic connectivity; more than 95% of vGluT1-immunolabeled terminals formed axo-spinous synapses in both conditions. In contrast, the prevalence of vGluT2-immunoreactive terminals did not change after MPTP treatment (21.7 +/- 1.3% vs. 21.6 +/- 1.2% total glutamatergic boutons). However, a substantial increase in the ratio of axo-spinous to axo-dendritic synapses formed by vGluT2-immunoreactive terminals was found in the pre-caudate and post-putamen striatal regions of MPTP-treated monkeys, suggesting a certain degree of synaptic reorganization of the thalamostriatal system in parkinsonism. About 20% of putative glutamatergic terminals did not show immunoreactivity in striatal tissue immunostained for both vGluT1 and vGluT2, suggesting the expression of another vGluT in these boutons. These findings provide striking evidence that suggests a differential degree of plasticity of the corticostriatal and thalamostriatal system in PD.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synaptic plasticity is the process by which long-lasting changes take place at synaptic connections. The phenomenon itself is complex and can involve many levels of organization. Some authors separate forms into adaptations that have positive or negative consequences for the individual. It has been hypothesized that an increase in the number of synapses may represent a structural basis for the enduring expression of synaptic plasticity during some events that involve memory and learning; also, it has been suggested that perforated synapses increase in number after some diseases and experimental situations. The aim of this study was to analyze whether dopamine depletion induces changes in the synaptology of the corpus striatum of rats after the unilateral injection of 6-OHDA. The findings suggest that after the lesion, both contralateral and ipsilateral striata exhibit an increased length of the synaptic ending in ipsilateral (since third day) and contralateral striatum (since Day 20), loss of axospinous synapses in ipsilateral striatum and a significant increment in the number of perforated synapses, suggesting brain plasticity that might be deleterious for the spines, because this type of synaptic contacts are presumably excitatory, and in the absence of the modulatory effects of dopamine, the neuron could die through excitotoxic mechanisms. Thus, we can conclude that the presence of perforated synapses after striatal dopamine depletion might be a form of maladaptive synaptic plasticity.
    Microscopy (Oxford, England). 09/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current concept of basal ganglia organization and function in physiological and pathophysiological conditions excludes the most numerous cells in the brain, i.e., the astrocytes, present with a ratio of 10:1 neuron. Their role in neurodegenerative condition such as Parkinson's disease (PD) remains to be elucidated. Before embarking into physiological investigations of the yet-to-be-identified "tripartite" synapses in the basal ganglia in general and the striatum in particular, we therefore characterized anatomically the PD-related modifications in astrocytic morphology, the changes in astrocytic network connections and the consequences on the spatial relationship between astrocytic processes and asymmetric synapses in normal and PD-like conditions in experimental and human PD. Our results unravel a dramatic regulation of striatal astrocytosis supporting the hypothesis of a key role in (dys) regulating corticostriatal transmission. Astrocytes and their various properties might thus represent a therapeutic target in PD.
    Frontiers in Aging Neuroscience 01/2014; 6:258. · 2.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the years since the discovery of dopamine in the neostriatum, we have learned much about the anatomy of this large subcortical nucleus. In rodents, it is one nucleus penetrated by many fibers from the cerebral cortex. In larger animals and in humans, the area is split by a bundle of mainly corticofugal axons into the caudate nucleus and putamen. Dopamine input to both is similar and except for the details of cortical afferents to the two parts the striatum seems to act as one structure. Its main function is expected to be the transfer of the information carried in its cortical inputs onward through the basal ganglia. Diseases of this area of brain are associated with movement disorders and much is made of the action of dopamine on the long-term stability of corticostriatal synapses. The cortex is not at all the only input to the area, however, and the thalamus has almost as many synapses with striatal output neurons as has the cortex. This chapter summarizes the contributions to the study of the involvement of thalamostriatal inputs presented at Dopamine 2013 and emphasizes that this input, though largely ignored, has important lessons for those interested in understanding the function of the basal ganglia.
    Progress in brain research 01/2014; 211:1-11. · 5.10 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014