scholarly journals Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

2009 ◽  
Vol 61 (4) ◽  
pp. 395-412 ◽  
Author(s):  
Clare M. Gladding ◽  
Stephen M. Fitzjohn ◽  
Elek Molnár
Keyword(s):  
Glutamate Receptor ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Depression ◽  
Metabotropic Glutamate

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.

Suppression of the glutamate receptor delta 2 subunit produces a specific impairment in cerebellar long-term depression

1996 ◽  
Vol 76 (5) ◽  
pp. 3578-3583 ◽  
Author(s):  
A. Jeromin ◽  
R. L. Huganir ◽  
D. J. Linden
Keyword(s):  
Glutamate Receptor ◽  
Antisense Oligonucleotide ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Calcium Influx ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Flow Through

1. The role of the glutamate receptor subunit delta 2 in the induction of cerebellar long-term depression (LTD) was investigated by application of antisense oligonucleotides. The delta 2 subunit is selectively localized to Purkinje cells (PCs), with the highest levels being in the PC dendritic spines, where parallel fibers are received and where cerebellar LTD is expressed. 2. Immunocytochemical analysis of calbindin-positive PCs revealed that both the dendritic and somatic expression of delta 2 was reduced in antisense-but not in sense-treated cultures. An antisense oligonucleotide directed against the related subunit delta 1 did not affect the expression of delta 2 in PCs. 3. Cerebellar LTD may be reliably induced in a preparation of cultured embryonic cerebellar neurons from the mouse when parallel and climbing fiber stimulation are replaced by brief glutamate pulses and strong, direct depolarization of the PC, respectively. Application of an antisense oligonucleotide directed against delta 2 completely blocked the induction of LTD produced by glutamate/ depolarization conjunctive stimulation. A delta 2 sense oligonucleotide or an antisense oligonucleotide directed against the related delta 1 subunit had no effect. 4. The effect of the delta 2 antisense oligonucleotide was not related to attenuation of calcium influx via voltage-gated channels or calcium mobilization via metabotropic glutamate receptors, as assessed with fura-2 microfluorimetry. Current flow through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-associated ion channels also appeared unaltered. All three of these processes have previously been shown to be required for cerebellar LTD induction. The observation that delta 2 is involved in a metabotropic-glutamate-receptor-independent signaling pathway that is required for LTD induction supports the view that delta 2 participates in the formation of a novel postsynaptic receptor complex.

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