The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Two distinct oscillatory states determined by the NMDA receptor in rat inferior olive
Open accessAbstract
1. The effects of N-methyl-D-aspartate (NMDA) receptor activation and blockade on subthreshold membrane potential oscillations of inferior olivary neurones were studied in brainstem slices from 12- to 21-day-old rats. 2. Dizocilpine (MK-801), a non-competitive NMDA antagonist, at 1-45 microM abolished spontaneous subthreshold oscillations, without affecting membrane potential, input resistance, or the low-threshold calcium current, I(T). Ketamine (100 microM), a non-competitive NMDA antagonist, and L-689,560 (20 microM), an antagonist at the glycine site of the NMDA receptor, also abolished the oscillations, while the competitive non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20-50 microM) had no effect. 3. NMDA (100 microM) induced 4.1 Hz subthreshold oscillations and reversibly depolarized olivary neurones by 13.7 mV. In contrast, 10 microM alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and 20 microM kainic acid depolarized the membrane equivalently but did not induce oscillations. 4. Both NMDA-induced and spontaneous subthreshold oscillations were unaffected by 1 microM tetrodotoxin and were prevented by substituting extracellular calcium with cobalt. 5. Removing magnesium from the perfusate did not affect spontaneous subthreshold oscillations but did prevent NMDA-induced oscillations. 6. NMDA-induced oscillations were resistant to 50 microM mibefradil, an I(T) blocker, in contrast to spontaneous oscillations. Both oscillations were inhibited by 20 microM nifedipine, an L-type calcium channel antagonist, and 200 nM omega-agatoxin IVA, a P-type calcium channel blocker. Bay K 8644 (10 microM), an L-type Ca(2+) agonist, significantly enhanced the amplitude of both spontaneous and NMDA-induced oscillations. 7. The data indicate that NMDA receptor activation induces olivary neurones to manifest high amplitude membrane potential oscillations in part mediated by L- and P- but not T-type calcium currents. Moreover, the data demonstrate that NMDA receptor currents are necessary for generation of spontaneous subthreshold oscillations in the inferior olive.
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“Serotonin and NMDA receptors within the IO can potently modulate cerebellar output, either by changing HCN and Cav3.1 channel activity after 5-HT2A receptor activation to modulate pacemaking [266, 267], or by changing spatial patterns of electrotonic coupling after NMDA receptor activation to regulate synchronous spiking in the cerebellum [268].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [267]
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Metadata
- Authors
- Placantonakis, D. G., & Welsh, J. P.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2001-07
- Volume
- 534
- Issue
- 1
- Pages
- 123-140
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2278697
- OpenAlex
- W2117510935
- Cited by
- 49
- References
- 52
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 8
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute of Neurological Disorders and Stroke (NS31224, R56NS031224, R01NS031224)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- inferior olive, NMDA receptor, L-type calcium channels, P-type calcium channels, T-type calcium current, glycine site antagonists, low-threshold calcium current, magnesium dependence, synaptic plasticity, cerebellar nuclei, brainstem slices, ketamine, MK-801
- MeSH terms
- Animals, Calcium, Differential Threshold, Electric Conductivity, Electrophysiology, Magnesium, Membrane Potentials, Neurons, Olivary Nucleus, Oscillometry, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Calcium Channels, L-Type, Calcium Channels, P-Type, Rats, In Vitro Techniques
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