Modulation of synaptic transmission and differential localisation of mGlus in cultured hippocampal autapses

Metabotropic glutamate receptors (mGlus) are known to modulate synaptic transmission 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 distribution of mGlus. Agonists at all three groups of mGlus depressed glutamatergic transmission, whereas only agonists at group I mGlus depressed GABAergic transmission. Agonists at all mGlus failed to modulate Ca2+ and K+ channels in glutamatergic autapses whereas an agonist at group III mGlus did depress the frequency of miniature excitatory postsynaptic currents (mEPSCs). Agonists failed to modulate Ca2+ or K+ channels and miniature inhibitory postsynaptic currents (mIPSCs) in GABAergic autapses. Distribution studies using selective antibodies revealed punctate staining for group III mGlus that co-localised with the synaptic marker, synaptophysin. Staining for the remaining mGlus was more diffuse throughout the soma and processes with little co-localisation with synaptophysin. The distribution of the group III receptors is consistent with the direct 'downstream' modulation of mEPSCs, although the exact mechanism of action for the remaining receptors remains unclear.