ArticleNeurobiology of disease2021
Facilitation of GluN2C-containing NMDA receptors in the external globus pallidus increases firing of fast spiking neurons and improves motor function in a hemiparkinsonian mouse model.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- GluN2C/D-containing NMDA receptors enhance temporal summation and increase sound-evoked and spontaneous firing in the inferior colliculus.The Journal of physiology · 2025Article
- Design of (Journal of medicinal chemistry · 2025Article
- GluN2D-containing NMDA receptors in parvalbumin neurons in the nucleus accumbens regulate nocifensive responses in neuropathic pain.Neurobiology of disease · 2025Article
- GluN2C/D-containing NMDA receptors enhance temporal summation and increase sound-evoked and spontaneous firing in the inferior colliculus.bioRxiv : the preprint server for biology · 2024Article
- Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/CaNeuroscience bulletin · 2024Article
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Simulating combined monoaminergic depletions in a PD animal model through a bio-constrained differential equations system.Frontiers in computational neuroscience · 2024Article
- GluN2D Subunit in Parvalbumin Interneurons Regulates Prefrontal Cortex Feedforward Inhibitory Circuit and Molecular Networks Relevant to Schizophrenia.Biological psychiatry · 2023Article
- External globus pallidus input to the dorsal striatum regulates habitual seeking behavior in male mice.Nature communications · 2023Article
- Cell and circuit complexity of the external globus pallidus.Nature neuroscience · 2023Review
- Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits.Nature structural & molecular biology · 2023Article
- Optogenetic Globus Pallidus Stimulation Improves Motor Deficits in 6-Hydroxydopamine-Lesioned Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Derivatives of (Journal of medicinal chemistry · 2022Article
- Discovery of (Frontiers in chemistry · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Globus pallidus externa (GPe) is a nucleus in the basal ganglia circuitry involved in the control of movement. Recent studies have demonstrated a critical role of GPe cell types in Parkinsonism. Specifically increasing the function of parvalbumin (PV) neurons in the GPe has been found to facilitate motor function in a mouse model of Parkinson's disease (PD). The knowledge of contribution of NMDA receptors to GPe function is limited. Here, we demonstrate that fast spiking neurons in the GPe express NMDA receptor currents sensitive to GluN2C/GluN2D-selective inhibitors and glycine site agonist with higher efficacy at GluN2C-containing receptors. Furthermore, using a novel reporter model, we demonstrate the expression of GluN2C subunits in PV neurons in the GPe which project to subthalamic nuclei. GluN2D subunit was also found to localize to PV neurons in GPe. Ablation of GluN2C subunit does not affect spontaneous firing of fast spiking neurons. In contrast, facilitating the function of GluN2C-containing receptors using glycine-site NMDA receptor agonists, D-cycloserine (DCS) or AICP, increased the spontaneous firing frequency of PV neurons in a GluN2C-dependent manner. Finally, we demonstrate that local infusion of DCS or AICP into the GPe improved motor function in a mouse model of PD. Together, these results demonstrate that GluN2C-containing receptors and potentially GluN2D-containing receptors in the GPe may serve as a therapeutic target for alleviating motor dysfunction in PD and related disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.