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1.
J Gen Intern Med ; 2020 Jun 09.
Article in English | MEDLINE | ID: mdl-32519324
5.
Eur J Neurosci ; 27(7): 1647-58, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18380666

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.


Subject(s)
Cerebral Cortex/physiology , Corpus Striatum/physiology , MPTP Poisoning/physiopathology , Neuronal Plasticity/physiology , Synapses/physiology , Thalamus/physiology , Animals , Cerebral Cortex/pathology , Corpus Striatum/pathology , Female , MPTP Poisoning/pathology , Macaca mulatta , Neural Pathways/pathology , Neural Pathways/physiology , Rats , Synapses/pathology , Thalamus/pathology
6.
J Comp Neurol ; 499(2): 231-43, 2006 Nov 10.
Article in English | MEDLINE | ID: mdl-16977615

ABSTRACT

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents.


Subject(s)
Afferent Pathways/physiology , Corpus Striatum/metabolism , Synapses/metabolism , Thalamus/metabolism , Vesicular Glutamate Transport Protein 2/metabolism , Afferent Pathways/cytology , Animals , Blotting, Western/methods , Corpus Striatum/anatomy & histology , Functional Laterality , Immunohistochemistry/methods , Male , Microscopy, Immunoelectron/methods , Models, Anatomic , Phytohemagglutinins/metabolism , Rats , Rats, Sprague-Dawley , Synapses/classification , Synapses/ultrastructure , Thalamus/anatomy & histology , Vesicular Glutamate Transport Protein 1/metabolism
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