ArticleThe Journal of physiology2011
Disruption of metabotropic glutamate receptor signalling is a major defect at cerebellar parallel fibre-Purkinje cell synapses in staggerer mutant mice.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Anti-Kv1.2 Immunoprecipitation Identifies shared mGluR1-Associated Signalosome Complex proteins and PKC-Mediated Regulation of Kv1.2 in the Cerebellum.bioRxiv : the preprint server for biology · 2025Article
- The spiny relationship between parallel fibers, climbing fibers, and Purkinje cells.Frontiers in physiology · 2025Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Pharmacologically targeting transient receptor potential channels for seizures and epilepsy: Emerging preclinical evidence of druggability.Pharmacology & therapeutics · 2023Review
- Article
- Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo.Communications biology · 2022Article
- TRPC channels as emerging targets for seizure disorders.Trends in pharmacological sciences · 2022Review
- Deletion of Class II ADP-Ribosylation Factors in Mice Causes Tremor by the Nav1.6 Loss in Cerebellar Purkinje Cell Axon Initial Segments.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy.Cerebellum (London, England) · 2019Review
- Expression of mutant DISC1 in Purkinje cells increases their spontaneous activity and impairs cognitive and social behaviors in mice.Neurobiology of disease · 2017Article
- Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice.The Journal of physiology · 2017Article
- Type-1 metabotropic glutamate receptor signaling in cerebellar Purkinje cells in health and disease.F1000Research · 2017Review
- Consensus Paper: Cerebellar Development.Cerebellum (London, England) · 2016Review
- Are Type 1 metabotropic glutamate receptors a viable therapeutic target for the treatment of cerebellar ataxia?The Journal of physiology · 2016Review
- RORα Regulates Multiple Aspects of Dendrite Development in Cerebellar Purkinje Cells In Vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- TRPC3-dependent synaptic transmission in central mammalian neurons.Journal of molecular medicine (Berlin, Germany) · 2015Review
- Induced pluripotent stem cell technology for modelling and therapy of cerebellar ataxia.Open biology · 2015Review
- Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism.Neuropharmacology · 2015Article
- The Moonwalker mouse: new insights into TRPC3 function, cerebellar development, and ataxia.Cerebellum (London, England) · 2014Review
- Mutant β-III spectrin causes mGluR1α mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staggerer mutant mice have functional loss of a transcription factor, retinoid-related orphan receptor α (RORα), which is abundantly expressed in Purkinje cells (PCs) of the cerebellum.Homozygous staggerer (sg/sg)mice show cerebellar hypoplasia and congenital ataxia. Sg/sg mice serve as an important extreme mouse model of the hereditary spinocerebellar ataxia type 1 (SCA1), since it has been shown that RORα dysfunction is strongly correlated with SCA1 pathogenesis. However, synaptic abnormalities, especially at parallel fibre (PF)-PC synapses, in SCA1-related sg/sg mice have not been examined in detail electrophysiologically. In this study, we report that PFs can still establish functional synapses onto PCs in sg/sg mice in spite of reduction in the number of PF-PC synapses. Compared with PF-evoked EPSCs in the wild-type or heterozygotes, the success rate of the EPSC recordings in sg/sg was quite low (∼40%) and the EPSCs showed faster kinetics and slightly decreased paired pulse facilitation at short intervals. The prominent synaptic dysfunction is that sg/sg mice lack metabotropic glutamate receptor (mGluR)-mediated slow EPSCs completely. Neither intense PF stimulation nor an exogenously applied mGluR agonist, DHPG, could elicit mGluR-mediated responses.Western blot analysis in the sg/sg cerebellum revealed low-level expression of mGluR1 and TRPC3, both of which underlie mGluR-mediated slow currents in PCs. Immunohistochemical data demonstrated marked mislocalization of mGluR1 on sg/sg PCs.We found that mGluR-mediated retrograde suppression of PF-PC EPSCs by endocannabinoid is also impaired completely in sg/sg mice. These results suggest that disruption of mGluR signalling at PF-PC synapses is one of the major synaptic defects in sg/sg mice and may manifest itself in SCA1 pathology.
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