Metabotropic glutamate receptor subtypes modulating neurotransmission at parallel fibre-Purkinje cell synapses in rat cerebellum

The actions of reportedly group-selective metabotropic glutamate (mGlu) rec eptor agonists and antagonists on neurotransmission at parallel fibre-Purki nje cell synapses in the rat cerebellum have been characterised using sharp microelectrode recording and an in vitro slice preparation. Application of the group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) or the group III selective agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed s ynaptic transmission in a reversible and concentration-dependent manner (EC 50=18 and 5 muM. respectively). The depression produced by DHPG was unrelat ed to the depolarisation observed in some Purkinje cells. The group II agon ist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 1 IJ-M) had no effect. The effects of DHPG were inhibited by the group I-selective ant agonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), but not by the group II/III antagonist alpha -methyl-4-phosphono phenylglycine (MPPG). The effect of L-AP4 was inhibited by MPPG, but not by the group I/II antagonist (S)-alpha -methyl-4-carboxyphenylglycine (MCPG). By themselves, the antagonists did not affect the EPSPs, suggesting that n either receptor is activated during low frequency neurotransmission. It is concluded that. in addition to the excitatory role for group I receptors de scribed previously, both group I and III (but not group II) mGlu receptors operate at this synapse to inhibit synaptic transmission. The specific rece ptor subtypes involved are likely to be mGlu1 and mGlu4. (C) 2001 Elsevier Science Ltd. All rights reserved.