Modulation of synaptic transmission and differential localisation of mGlusin cultured hippocampal autapses

Metabotropic glutamate receptors (mGlus) are known to modulate synaptic tra nsmission in various pathways of the central nervous system, but the exact mechanisms by which this modulation occurs remain unclear. Here we utilise electrophysiological and immunocytochemical techniques on cultured autaptic hippocampal neurones to investigate the mechanism of action and distributi on of mGlus. Agonists at all three groups of mGlus depressed glutamatergic transmission, whereas only agonists at group I mGlus depressed GABAergic tr ansmission. Agonists at all mGlus failed to modulate Ca2+ and K+ channels i n glutamatergic autapses whereas an agonist at group III mGlus did depress the frequency of miniature excitatory postsynaptic currents (mEPSCs). Agoni sts failed to modulate Ca2+ or K+ channels and miniature inhibitory postsyn aptic currents (mIPSCs) in GABAergic autapses. Distribution studies using s elective antibodies revealed punctate staining for group III mGlus that co- localised with the synaptic marker, synaptophysin. Staining for the remaini ng mGlus was more diffuse throughout the soma and processes with little co- localisation with synaptophysin. The distribution of the group III receptor s is consistent with the direct 'downstream' modulation of mEPSCs, although the exact mechanism of action for the remaining receptors remains unclear. (C) 1999 Elsevier Science Ltd. All rights reserved.