Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex

The role of group III metabotropic glutamate receptors (mGluRs) in modulati ng excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic curren ts (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-ph osphonobutyric acid (L-AP4, 500 mu M) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/ mEPSC) event freq uency. Thr facilitatory effect of L-AP4 (100 mu M) on sEPSC frequency preva iled in the presence of DL-2-amino-5-phosphonopentanoic acid (100 mu M) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophen ylglycine (20 mu M). These data confirmed that group III mGluRs, and not N- methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclope ntane-1,2, 4-tricarboxylic acid (20 mu M) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L -AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs record ed in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic tr ansmission in layer V cells of the EC. The effect on mEPSCs suggests that t his receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a dire ct facilitatory action of group III mGluRs on synaptic transmission. In lay er II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.