MULTIPLE PRESYNAPTIC METABOTROPIC GLUTAMATE RECEPTORS MODULATE EXCITATORY AND INHIBITORY SYNAPTIC TRANSMISSION IN HIPPOCAMPAL AREA CA1

The metabotropic glutamate receptors (mGluRs) have many important role s in regulation of neuronal excitability and synaptic transmission. in hippocampal area CA1, activation of mGluRs can reduce both excitatory and inhibitory synaptic transmission. The conventional view is that t he presynaptic effects are mediated by L-2-amino-4-phosphonobutyric ac id (L-AP4)-sensitive, or group III mGluRs (mGluR4, mGluR6, mGluR7, mGl uR8). However, some studies suggest that other mGluR subtypes may also be involved in regulation of excitatory and inhibitory synaptic trans mission in area CA1. We have found that two pharmacologically distinct presynaptic receptors are involved in the depression of excitatory tr ansmission at the Schaffer collateral-CA1 synapse. Consistent with pre vious studies, one receptor subtype is an L-AP4-sensitive receptor tha t is pharmacologically similar to mGluR4 or mGluR7. However, we have f ound that a second mGluR subtype, which is pharmacologically similar t o mGluR1 and mGluR5 (group I mGluRs), can also reduce excitatory synap tic transmission in area CA1. Analysis of effects of agonists of these two receptors on miniature EPSCs and paired-pulse facilitation sugges t that both receptors are localized presynaptically. It is also shown that the mGluR that reduces transmission at inhibitory synapses in are a CA1 is presynaptically localized, is insensitive to L-AP4, and is se nsitive to agonists selective for mGluR1 and mGluR5.