Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons

Chu, Hong-Yuan; McIver, Eileen L.; Kovaleski, Ryan F.; Atherton, Jeremy F.; Bevan, Mark D.

doi:10.1016/j.neuron.2017.08.038

Cited by 111 publications

(204 citation statements)

References 68 publications

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“…Our findings also suggest a trend towards a larger proportion of pallidal terminals in contact with dendrites of GABAergic interneurons in parkinsonian monkeys compared with controls. The pruning and morphological changes of corticothalamic terminals seen in parkinsonian monkeys are reminiscent of previous findings from our group and others about corticostriatal and corticosubthalamic terminals in MPTP‐treated monkeys, and in 6‐hydroxydopamine‐treated rodents (Chu et al, ; Day et al, ; Ingham et al, ; Mathai et al, ; Mathai & Smith, ; Raju et al, ; Villalba et al, ; Villalba et al, ; Villalba & Smith, ; Villalba & Smith, ).…”

Section: Discussionsupporting

confidence: 80%

“…We compared the relative prevalence, pattern of synaptic connec- rodents (Chu et al, 2017;Day et al, 2006;Ingham et al, 1998;Mathai et al, 2015;Mathai & Smith, 2011;Raju et al, 2008;Villalba et al, 2009;Villalba et al, 2015;Villalba & Smith, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in the striatum and subthalamic nucleus (STN), the dopamine‐depleted state is accompanied by substantial remodeling of specific synaptic microcircuits. In particular, significant changes in the number and ultrastructural features of cortical terminals, associated with robust alterations in electrophysiological and plastic properties of corticostriatal and corticosubthalamic synapses have been reported in rodent and primate models of PD (Chu, McIver, Kovaleski, Atherton, & Bevan, ; Day et al, ; Ingham, Hood, Taggart, & Arbuthnott, ; Mathai et al, ; Mathai & Smith, ; Raju et al, ; Villalba, Lee, & Smith, ; Villalba, Mathai, & Smith, ; Villalba & Smith, ; Villalba & Smith, ). In the STN of dopamine‐depleted mice, there is a significant increase in the number of synapses formed by individual GABAergic terminals from the external segment of the globus pallidus (GPe), accompanied with increased synaptic strength of pallidosubthalamic synapses (Chu et al, ; Fan, Baufreton, Surmeier, Chan, & Bevan, ).…”

Section: Introductionmentioning

confidence: 99%

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Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys

Swain¹,

Galván

Wichmann

et al. 2019

J of Comparative Neurology

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In the primate thalamus, the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM) receive GABAergic projections from the internal globus pallidus (GPi) and glutamatergic inputs from motor cortices. In this study, we used electron microscopy to assess potential structural changes in GABAergic and glutamatergic microcircuits in the VApc and CM of MPTP‐treated parkinsonian monkeys. The intensity of immunostaining for GABAergic markers in VApc and CM did not differ between control and parkinsonian monkeys. In the electron microscope, three major types of terminals were identified in both nuclei: (a) vesicular glutamate transporter 1 (vGluT1)‐positive terminals forming asymmetric synapses (type As), which originate from the cerebral cortex, (b) GABAergic terminals forming single symmetric synapses (type S1), which likely arise from the reticular nucleus and GABAergic interneurons, and (c) GABAergic terminals forming multiple symmetric synapses (type S2), which originate from GPi. The density of As terminals outnumbered that of S1 and S2 terminals in VApc and CM of control and parkinsonian animals. No significant change was found in the abundance and synaptic connectivity of S1 and S2 terminals in VApc or CM of MPTP‐treated monkeys, while the prevalence of “As” terminals in VApc of parkinsonian monkeys was 51.4% lower than in controls. The cross‐sectional area of vGluT1‐positive boutons in both VApc and CM of parkinsonian monkeys was significantly larger than in controls, but their pattern of innervation of thalamic cells was not altered. Our findings suggest that the corticothalamic system undergoes significant synaptic remodeling in the parkinsonian state.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys

Swain¹,

Galván

Wichmann

et al. 2019

J of Comparative Neurology

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show abstract

“…The STN is a site of prominent alterations in glutamatergic transmission (Chu 2015 and Chu 2017), which may contribute to increased firing, increased burst firing, and the development of alpha- and beta-band oscillations in firing in the STN which are typical for the parkinsonian state (Galvan 2008, Pan 2014 and Pan 2016). …”

Section: Discussionmentioning

confidence: 99%

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

Bhattacharya

Dunn

et al. 2018

J of Neuroscience Research

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N-methyl-D-aspartate receptors (NMDARs) are ion channels comprising tetrameric assemblies of GluN1 and GluN2 receptor subunits that mediate excitatory neurotransmission in the central nervous system. Of the four different GluN2 subunits, the GluN2D subunit-containing NMDARs have been suggested as a target for antiparkinsonian therapy because of their expression pattern in some of the basal ganglia nuclei that show abnormal firing patterns in the parkinsonian state, specifically the subthalamic nucleus (STN). In this study, we demonstrate that blockade of NMDARs altered spike firing in the STN in a male nonhuman primate that had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In accompanying experiments in male rodents, we found that GluN2D-NMDAR expression in the STN was reduced in acutely or chronically dopamine-depleted animals. Taken together, our data suggest that blockade of NMDARs in the STN may be a viable antiparkinsonian strategy, but that the ultimate success of this approach may be complicated by parkinsonism-associated changes in NMDAR expression in the STN.

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“…Excessive GP i neuronal activity breaks the thalamocortical system, which inhibits movement and causes hypokinetic features or parkinsonian symptoms. In addition, the cortico‐ STN transmission strength in the hyperdirect pathway diminishes significantly after dopamine loss, which contributes to motor dysfunction in PD (Chu et al ., ). In this model of the parkinsonian state, thin and thick arrows show the proposed decrease and increase in neuronal activities (firing frequency) for specific connections.…”

Section: Introductionmentioning

confidence: 99%

Oscillatory activity in the cortico‐basal ganglia‐thalamic neural circuits in Parkinson's disease

Singh

2018

Eur J of Neuroscience

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Dopamine is an important neurotransmitter that maintains the balance within the basal ganglia between the direct pathway, which promotes movement, and the indirect pathway, which inhibits movement. Degeneration of dopaminergic neurons in the substantia nigra increases the influence of the indirect pathway, resulting in motor dysfunction in Parkinson's disease (PD). The direct and indirect pathways are composed of basal ganglia and thalamic nuclei, which are interconnected via independent parallel loop circuits with cortical areas and often referred to as cortico-basal ganglia-thalamic (CBT) neural circuits. CBT circuits have been useful in generating hypotheses to describe slowness in PD. Recent work has focused on aberrant neural oscillations within CBT circuits. Although beta (13-30 Hz) oscillations are a common feature of the CBT network, there is growing evidence that abnormally exaggerated beta oscillations, observed after dopamine loss in the CBT circuits, may contribute to motor symptoms of PD. Disruption of abnormal beta oscillations has been associated with the improvement of motor functions during pharmacological treatments, surgical lesions, and electrical stimulation. However, it is not clear how abnormal oscillations originate in the CBT motor network and resonate specifically in the beta band after the loss of dopamine. Most studies have addressed these questions by simultaneous recordings of oscillations in the motor cortex, basal ganglia nuclei, and motor regions of the thalamus in animal models of parkinsonism as well as in PD patients. This review further discusses previous and current studies of the changes in oscillatory activity at the level of CBT neural network in PD.

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Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons

Cited by 111 publications

References 68 publications

Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys

Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys

NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate

Oscillatory activity in the cortico‐basal ganglia‐thalamic neural circuits in Parkinson's disease

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