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Disruption of metabotropic glutamate receptor signalling is a major defect at cerebellar parallel fibre–Purkinje cell synapses in staggerer mutant mice
Author(s) -
Mitsumura Kazuhiro,
Hosoi Nobutake,
Furuya Nobuhiko,
Hirai Hirokazu
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.207563
Subject(s) - purkinje cell , neuroscience , metabotropic glutamate receptor , parallel fiber , cerebellum , biology , glutamate receptor , neurotransmission , metabotropic glutamate receptor 4 , cerebellar cortex , chemistry , receptor , biochemistry
Non‐technical summary Homozygous staggerer mutant ( sg / sg ) mice exhibit cerebellar atrophy and congenital ataxia, and serve as an important extreme mouse model of the hereditary spinocerebellar ataxia type 1 (SCA1), since the staggerer mutation is closely related to SCA1 pathology. However, we know little about synaptic abnormalities at cerebellar parallel fibre (PF)–Purkinje cell (PC) synapses in sg / sg mice, which could underlie SCA1 pathology. In this study, we report that PFs still make reasonably functional fast synapses onto PCs in sg / sg mice despite reduction in the number of PF–PC synapses. In contrast, sg / sg mice lack metabotropic glutamate receptor (mGluR)‐mediated slow synaptic transmission completely. Synaptic modulation caused by mGluR‐mediated endocannabinoid release is also abolished at sg / sg PF–PC synapses. Our results indicate that major synaptic abnormality is disruption of cerebellar mGluR signalling in SCA1‐related sg / sg mice, and that mGluR signalling can be one of the key factors to SCA1 pathology.