Premium
Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex
Author(s) -
Lorez Matthias,
Humbel Urs,
Pflimlin MarieClaire,
Kew James N C
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705099
Subject(s) - metabotropic glutamate receptor , autoreceptor , excitatory postsynaptic potential , neuroscience , glutamate receptor , postsynaptic potential , chemistry , agonist , long term potentiation , long term depression , post tetanic potentiation , inhibitory postsynaptic potential , biology , receptor , ampa receptor , biochemistry
Group III metabotropic glutamate receptors (mGluRs) of the subtype 4a are localized within presynaptic active zones of cerebellar parallel fibre (PF)‐Purkinje cell (PC) synapses. In order to investigate the conditions necessary for group III mGluR autoreceptor‐activation by synaptically released glutamate, we characterized the effects of selective agonists and antagonists on excitatory postsynaptic currents (EPSCs) evoked by several distinct PF stimulation patterns. The group III mGluR‐selective agonist L‐AP4 depressed evoked EPSCs at PF‐PC synapses in rat brain slices with an EC 50 of 2.4 μ M and maximum inhibition of 80%. This L‐AP4‐induced depression was antagonized by the group III mGluR‐selective antagonist MSOP with an estimated equilibrium dissaciation constant of 12.5 μ M . Paired‐pulse or four‐pulse PF stimulations did not activate presynaptic group III mGluRs as revealed by the lack of effect of 1 m M MSOP on relative test EPSC amplitudes with latencies of 250–500 ms. The potentiation of a test EPSC evoked 200–500 ms after a short tetanic burst (100 Hz for 60 ms), was also unchanged in the presence of MSOP. Endogenous autoreceptor‐activation was revealed only during prolonged stimulation trains (10 Hz for 4.4 s), where, in the presence of 1 m M MSOP, the EPSC amplitudes were enhanced by 15%. These observations support an autoreceptor function of group III mGluRs and a role in short‐term synaptic plasticity at PF synapses. However, the low to moderate activation levels observed, despite the close spatial relation with glutamate release sites, suggests that additional mechanisms regulate receptor activation.British Journal of Pharmacology (2003) 138 , 614–625. doi: 10.1038/sj.bjp.0705099