Di. Evans et al., Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex, J NEUROPHYS, 83(5), 2000, pp. 2519-2525
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.