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Morphological changes of glutamatergic synapses in animal models of Parkinson's disease.

Villalba RM, Mathai A, Smith Y - Front Neuroanat (2015)

Bottom Line: More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys.The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered.Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

View Article: PubMed Central - PubMed

Affiliation: Yerkes National Primate Research Center, Emory University Atlanta, GA, USA ; UDALL Center of Excellence for Parkinson's Disease, Emory University Atlanta, GA, USA.

ABSTRACT
The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson's disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

No MeSH data available.


Related in: MedlinePlus

Schematic showing morphological changes in dendritic spines and glutamatergic afferents in striatal MSNs and projection neurons in the STN in MPTP-treated parkinsonian monkeys. In the striatum of parkinsonian monkeys, there is a significant reduction in the density of Sp on MSNs, but the remaining spines and terminals display an increase in volume. The size of the PSD at corticostriatal and thalamostriatal synapses is also increased and more commonly perforated in parkinsonian animals than controls. In the STN, there is an overall decrease in the prevalence of vGluT1-positive cortical terminals in contact with dendrites and spines of STN neurons in parkinsonian animals. Potential changes in the ultrastructure of spines and afferent glutamatergic terminals, as shown in the striatum, remain to be determined in the STN.
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Figure 4: Schematic showing morphological changes in dendritic spines and glutamatergic afferents in striatal MSNs and projection neurons in the STN in MPTP-treated parkinsonian monkeys. In the striatum of parkinsonian monkeys, there is a significant reduction in the density of Sp on MSNs, but the remaining spines and terminals display an increase in volume. The size of the PSD at corticostriatal and thalamostriatal synapses is also increased and more commonly perforated in parkinsonian animals than controls. In the STN, there is an overall decrease in the prevalence of vGluT1-positive cortical terminals in contact with dendrites and spines of STN neurons in parkinsonian animals. Potential changes in the ultrastructure of spines and afferent glutamatergic terminals, as shown in the striatum, remain to be determined in the STN.

Mentions: Striatal spine loss has been reported in the striatum of various animal models of PD and in parkinsonian patients. In both MPTP-treated monkeys and PD patients, the extent of spine pruning is tightly correlated with the extent of striatal dopaminergic denervation (Ingham et al., 1989; Stephens et al., 2005; Zaja-Milatovic et al., 2005; Smith and Villalba, 2008; Smith et al., 2009b; Villalba et al., 2009; Toy et al., 2014; Figures 1A,B, 4).


Morphological changes of glutamatergic synapses in animal models of Parkinson's disease.

Villalba RM, Mathai A, Smith Y - Front Neuroanat (2015)

Schematic showing morphological changes in dendritic spines and glutamatergic afferents in striatal MSNs and projection neurons in the STN in MPTP-treated parkinsonian monkeys. In the striatum of parkinsonian monkeys, there is a significant reduction in the density of Sp on MSNs, but the remaining spines and terminals display an increase in volume. The size of the PSD at corticostriatal and thalamostriatal synapses is also increased and more commonly perforated in parkinsonian animals than controls. In the STN, there is an overall decrease in the prevalence of vGluT1-positive cortical terminals in contact with dendrites and spines of STN neurons in parkinsonian animals. Potential changes in the ultrastructure of spines and afferent glutamatergic terminals, as shown in the striatum, remain to be determined in the STN.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585113&req=5

Figure 4: Schematic showing morphological changes in dendritic spines and glutamatergic afferents in striatal MSNs and projection neurons in the STN in MPTP-treated parkinsonian monkeys. In the striatum of parkinsonian monkeys, there is a significant reduction in the density of Sp on MSNs, but the remaining spines and terminals display an increase in volume. The size of the PSD at corticostriatal and thalamostriatal synapses is also increased and more commonly perforated in parkinsonian animals than controls. In the STN, there is an overall decrease in the prevalence of vGluT1-positive cortical terminals in contact with dendrites and spines of STN neurons in parkinsonian animals. Potential changes in the ultrastructure of spines and afferent glutamatergic terminals, as shown in the striatum, remain to be determined in the STN.
Mentions: Striatal spine loss has been reported in the striatum of various animal models of PD and in parkinsonian patients. In both MPTP-treated monkeys and PD patients, the extent of spine pruning is tightly correlated with the extent of striatal dopaminergic denervation (Ingham et al., 1989; Stephens et al., 2005; Zaja-Milatovic et al., 2005; Smith and Villalba, 2008; Smith et al., 2009b; Villalba et al., 2009; Toy et al., 2014; Figures 1A,B, 4).

Bottom Line: More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys.The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered.Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

View Article: PubMed Central - PubMed

Affiliation: Yerkes National Primate Research Center, Emory University Atlanta, GA, USA ; UDALL Center of Excellence for Parkinson's Disease, Emory University Atlanta, GA, USA.

ABSTRACT
The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson's disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined.

No MeSH data available.


Related in: MedlinePlus