The Journal of Neurophysiology Vol. 83 No. 5 May 2000, pp. 2519-2525
Copyright ©2000 by the American Physiological Society

Activation of Presynaptic Group III Metabotropic Receptors Enhances Glutamate Release in Rat Entorhinal Cortex

Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Evans, D. Ieuan, Roland S. G. Jones, and Gavin Woodhall. Activation of Presynaptic Group III Metabotropic Receptors Enhances Glutamate Release in Rat Entorhinal Cortex. J. Neurophysiol. 83: 2519-2525, 2000. The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (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-phosphonobutyric acid (L-AP4, 500 µM) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 µM) on sEPSC frequency prevailed in the presence of DL2-amino-5-phosphonopentanoic acid (100 µM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 µM). 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-aminocyclopentane-1,2,4-tricarboxylic acid (20 µM) 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 recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this 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 direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.