Faculty Opinions recommendation of Mutant ataxin-3 with an abnormally expanded polyglutamine chain disrupts dendritic development and metabotropic glutamate receptor signaling in mouse cerebellar Purkinje cells.

2017 ◽  
Author(s):  
Masanobu Kano
Keyword(s):  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Signaling ◽  
Metabotropic Glutamate ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

scholarly journals Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination

2015 ◽  
Vol 112 (50) ◽  
pp. 15474-15479 ◽  
Author(s):  
Liang Zhou ◽  
Dong Yang ◽  
De-Juan Wang ◽  
Ya-Jun Xie ◽  
Jia-Huan Zhou ◽  
...  
Keyword(s):  
Cell Fate ◽  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Motor Coordination ◽  
Metabotropic Glutamate Receptor ◽  
Constitutive Expression ◽  
Metabotropic Glutamate ◽  
Associated Proteins ◽  
Cerebellar Purkinje Cells

Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber–PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.

scholarly journals Type-1 metabotropic glutamate receptor signaling in cerebellar Purkinje cells in health and disease

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 416 ◽  
Author(s):  
Masanobu Kano ◽  
Takaki Watanabe
Keyword(s):  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Synaptic Response ◽  
Coordination Control ◽  
Metabotropic Glutamate ◽  
Health And Disease ◽  
Output Neurons ◽  
Cerebellar Purkinje Cells

The cerebellum is a brain structure involved in coordination, control, and learning of movements, as well as certain aspects of cognitive function. Purkinje cells are the sole output neurons from the cerebellar cortex and therefore play crucial roles in the overall function of the cerebellum. The type-1 metabotropic glutamate receptor (mGluR1) is a key “hub” molecule that is critically involved in the regulation of synaptic wiring, excitability, synaptic response, and synaptic plasticity of Purkinje cells. In this review, we aim to highlight how mGluR1 controls these events in Purkinje cells. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunctions in several clinically relevant mouse models of human ataxias.

Potentiation of mossy fiber-evoked EPSPs in turtle cerebellar Purkinje cells by the metabotropic glutamate receptor agonist 1S,3R-ACPD

1992 ◽  
Vol 67 (4) ◽  
pp. 1006-1008 ◽  
Author(s):  
G. A. Kinney ◽  
N. T. Slater
Keyword(s):  
Nmda Receptor ◽  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Nmda Receptor Antagonist ◽  
Metabotropic Glutamate ◽  
Cerebellar Purkinje Cells ◽  
Glutamate Receptor Agonist

1. The effects of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje cells. 2. 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF-evoked EPSPs and revealed a late, slow EPSP component, but was without effect on PF-evoked EPSPs. The potentiation of both components of MF-evoked EPSPs was dose dependent, with an ED50 of approximately 3 microM. At higher doses (15-25 microM) 1S,3R-ACPD produced a direct depolarization of Purkinje cells in 57% of cells examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (AP-5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1 mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. The results demonstrate that mGluR activation by 1S,3R-ACPD produces a potent, stereospecific facilitation of NMDA receptor-mediated transmission at the MF-granule cell synapse.

scholarly journals Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination

2008 ◽  
Vol 363 (1500) ◽  
pp. 2173-2186 ◽  
Author(s):  
Masanobu Kano ◽  
Kouichi Hashimoto ◽  
Toshihide Tabata
Keyword(s):  
Signal Transduction ◽  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Cerebellar Purkinje Cells

The cerebellum is a brain structure involved in the coordination, control and learning of movements, and elucidation of its function is an important issue. Japanese scholars have made seminal contributions in this field of neuroscience. Electrophysiological studies of the cerebellum have a long history in Japan since the pioneering works by Ito and Sasaki. Elucidation of the basic circuit diagram of the cerebellum in the 1960s was followed by the construction of cerebellar network theories and finding of their neural correlates in the 1970s. A theoretically predicted synaptic plasticity, long-term depression (LTD) at parallel fibre to Purkinje cell synapse, was demonstrated experimentally in 1982 by Ito and co-workers. Since then, Japanese neuroscientists from various disciplines participated in this field and have made major contributions to elucidate molecular mechanisms underlying LTD. An important pathway for LTD induction is type-1 metabotropic glutamate receptor (mGluR1) and its downstream signal transduction in Purkinje cells. Sugiyama and co-workers demonstrated the presence of mGluRs and Nakanishi and his pupils identified the molecular structures and functions of the mGluR family. Moreover, the authors contributed to the discovery and elucidation of several novel functions of mGluR1 in cerebellar Purkinje cells. mGluR1 turned out to be crucial for the release of endocannabinoid from Purkinje cells and the resultant retrograde suppression of transmitter release. It was also found that mGluR1 and its downstream signal transduction in Purkinje cells are indispensable for the elimination of redundant synapses during post-natal cerebellar development. This article overviews the seminal works by Japanese neuroscientists, focusing on mGluR1 signalling in cerebellar Purkinje cells.

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