ArticleThe European journal of neuroscience2015
Mechanisms regulating spill-over of synaptic glutamate to extrasynaptic NMDA receptors in mouse substantia nigra dopaminergic neurons.
Article in The European journal of neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- NMDA receptor mediated tonic excitatory currents are elicited by EAAT inhibition on human neocortical pyramidal neurons.Frontiers in synaptic neuroscience · 2026Article
- Ceftriaxone alleviates mitochondrial damage through the inhibition of extrasynaptic NMDA receptor-mediated changes in intracellular calcium levels to improve cognitive deficits in APP/PS1 mice.Alzheimer's research & therapy · 2025Article
- Pharmacological Activation of Piezo1 Channels Enhances Astrocyte-Neuron Communication via NMDA Receptors in the Murine Neocortex.International journal of molecular sciences · 2024Article
- Tonic Activation of NR2D-Containing NMDARs Exacerbates Dopaminergic Neuronal Loss in MPTP-Injected Parkinsonian Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Deficits in integrative NMDA receptors caused by Grin1 disruption can be rescued in adulthood.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Impact of the gut microbiome on nicotine's motivational effects and glial cells in the ventral tegmental area in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Attenuation of Stimulated Accumbal Dopamine Release by NMDA Is Mediated through Metabotropic Glutamate Receptors.ACS chemical neuroscience · 2023Article
- Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain.Frontiers in synaptic neuroscience · 2023Review
- mGluR1α expression in the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus in Alzheimer's disease.IBRO neuroscience reports · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Article
- GluN2D NMDA Receptors Gate Fear Extinction Learning and Interneuron Plasticity.Frontiers in synaptic neuroscience · 2021Article
- Jacob, a Synapto-Nuclear Protein Messenger Linking N-methyl-D-aspartate Receptor Activation to Nuclear Gene Expression.Frontiers in synaptic neuroscience · 2021Review
- Pathophysiological Ionotropic Glutamate Signalling in Neuroinflammatory Disease as a Therapeutic Target.Frontiers in neuroscience · 2021Review
- Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.Cellular and molecular life sciences : CMLS · 2018Review
- Altered Synaptic and Extrasynaptic NMDA Receptor Properties in Substantia Nigra Dopaminergic Neurons From Mice Lacking the GluN2D Subunit.Frontiers in cellular neuroscience · 2018Article
- Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson's and Other Neurodegenerative Diseases.Frontiers in neuroscience · 2018Review
- Fasudil Enhances Therapeutic Efficacy of Neural Stem Cells in the Mouse Model of MPTP-Induced Parkinson's Disease.Molecular neurobiology · 2017Article
- Extrasynaptic NMDA receptor dependent long-term potentiation of hippocampal CA1 pyramidal neurons.Scientific reports · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
N-Methyl-D-aspartate glutamate receptors (NMDARs) contribute to neural development, plasticity and survival, but they are also linked with neurodegeneration. NMDARs at synapses are activated by coincident glutamate release and depolarization. NMDARs distal to synapses can sometimes be recruited by 'spill-over' of glutamate during high-frequency synaptic stimulation or when glutamate uptake is compromised, and this influences the shape of NMDAR-mediated postsynaptic responses. In substantia nigra dopamine neurons, activation of NMDARs beyond the synapse during different frequencies of presynaptic stimulation has not been explored, even though excitatory afferents from the subthalamic nucleus show a range of firing frequencies, and these frequencies change in human and experimental Parkinson's disease. This study reports that high-frequency stimulation (80 Hz/200 ms) evoked NMDAR-excitatory postsynaptic currents (EPSCs) that were larger and longer lasting than those evoked by single stimuli at low frequency (0.1 Hz). MK-801, which irreversibly blocked NMDAR-EPSCs activated during 0.1-Hz stimulation, left a proportion of NMDAR-EPSCs that could be activated by 80-Hz stimulation and that may represent activity of NMDARs distal to synapses. TBOA, which blocks glutamate transporters, significantly increased NMDAR-EPSCs in response to 80-Hz stimulation, particularly when metabotropic glutamate receptors (mGluRs) were also blocked, indicating that recruitment of NMDARs distal to synapses is regulated by glutamate transporters and mGluRs. These regulatory mechanisms may be essential in the substantia nigra for restricting glutamate diffusion from synaptic sites and keeping NMDAR-EPSCs in dopamine neurons relatively small and fast. Failure of glutamate transporters may contribute to the declining health of dopamine neurons during pathological conditions.
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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.