The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Ca V 3.1 is a tremor rhythm pacemaker in the inferior olive
Open accessAbstract
The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of Ca V 3.1 T-type Ca 2+ channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking Ca V 3.1 gene. Intracellular recordings in brain-stem slices revealed that the Ca V 3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of Ca V 3.1 gene in the inferior olive by sh RNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate Ca V 3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, Ca V 3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor.
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“Moreover, T-type calcium channels are a powerful mechanism by which the IO regulates cerebellar output [269].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [269]
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Items 101–142 of 142
Inferior Olive: All Ins and Outs
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“…near resting membrane potentials generates low-threshold Ca 2+ spikes responsible for the conspicuous burst firing and low-frequency oscillatory discharges observed in thalamic, olivary, and cerebellar neurons ( Park et al., 2010 ; Dreyfus et al., 2010 ; Molineux et al., 2006 ; Lee et al., 2014 ).”
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“17 oscillations have been postulated to be functionally related to the manifestations of pathological rhythmic bursts, such as myoclonus, convulsion, and tremor [18, 19, 26].”
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BackgroundNodding behavior couples to vigilance fluctuation in a high-calorie diet model of drowsiness
Shin, A., Woo, J., Kim, J. E., & Kim, D. (2018) · Molecular Brain · doi:10.1186/s13041-018-0377-4 · Cited by 4
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MethodResultSelf-citationSultan, Z. W., Najac, M., & Raman, I. M. (2024) · The Journal of Physiology · doi:10.1113/jp286818 · Cited by 4
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“…to previous studies (Amrutkar et al., 2020; Hutchinson et al., 2007) or more sensitive than others (Da Fonseca et al., 2001; Martin et al., 2005; Paterson et al., 2009), except for one study, which detected tremors in task-dependent voluntary forelimb movements under restraint (Stanford and…”
BackgroundMethodResultInfluentialIs essential tremor a degenerative or an electrical disorder? Electrical disorder
Cho, H. J. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.02.004 · Cited by 2
Baumel, Y., Yamin, H. G., & Cohen, D. (2023) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2023.1135799 · Cited by 2
“Many studies have reported the occurrence of highly synchronized, coherent oscillations in the theta band frequency in the cerebellar cortex during harmaline-induced body tremor (Llinas and Volkind, 1973; Milner et al., 1995; Jacobson et al., 2009; Park et al., 2010).”
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“…subtype-speci fi c blockers, knock-out (KO) mice have enabled the identi fi cation of subtype-speci fi c roles to circuit functions and associated behaviors (Kim et al., 2001; Lee et al., 2004; Becker et al., 2008; Park et al., 2010; Chen et al., 2012; Astori and Luthi, 2013; Gangarossa et al., 2014).”
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Bazzigaluppi, P. (2013) · EUR Research Repository (Erasmus University Rotterdam) · Cited by 2
GABAergic neuronal dysfunction underlies tremor in spinocerebellar ataxia 3
Banerjee, A., Chatterjee, M., Tan, K. J., Tay, S. H., Duan, K., Andiappan, A. K., Howland, S. W., Aso, Y., & Aw, S. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.052329 · Cited by 1
“The primary sites of dysfunction in ET are thought to be the inferior olive in the brainstem (Park et al., 2010) and the cerebellum (Louis et al., 2014) (although other brain regions have been implicated).”
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RNA Interference of GluN1 Inhibits Neuronal Rhythmogenesis in the Adult Inferior Olive
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InfluentialDynamics of the Inferior Olive Oscillator and Cerebellar Function
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Loyola, S., Bosman, L. W. J., Gruijl, J. R. D., de Jeu, M. T. G., Negrello, M., Hoogland, T. M., & Zeeuw, C. I. D. (2021) · Springer eBooks · doi:10.1007/978-3-030-23810-0_43 · Cited by 2
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“Tremor monitors used included a commercial model (San Diego Instruments, San Diego, CA, USA) as well as a custom built model that was inspired by a previously used design (30).”
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Kostadinov, D., Mathy, A., & Clark, B. A. (2019) · Springer eBooks · doi:10.1007/978-3-319-97911-3_44-2
Gap Junctions and Neuronal Synchronization in the Olivocerebellar System
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Metadata
- Authors
- Park, Y.-G., Park, H.-Y., Lee, C. J., Choi, S., Jo, S., Choi, H., Kim, Y.-H., Shin, H.-S., Llinas, R. R., & Kim, D.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Korea Institute of Science and Technology (KR)
- New York University (US)
- Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-05-24
- Volume
- 107
- Issue
- 23
- Pages
- 10731-10736
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2890811
- OpenAlex
- W2075318347
- Cited by
- 142
- References
- 45
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 15 · 2018: 7 · 2017: 8 · 2016: 2 · 2015: 12 · 2014: 12 · 2013: 9 · 2012: 16
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science and Technology
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 13742, P01NS013742)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Cav3.1, T-type calcium channels, inferior olive, essential tremor, pathological tremor, pacemaker neurons, harmaline, neural oscillations, shRNA knockdown
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Harmaline, Humans, Male, Mice, Inbred C57BL, Olivary Nucleus, Tremor, Mice, Knockout, Calcium Channels, T-Type, RNA Interference, Mice
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