Potentiation of synaptic transmission in the rat dentate gyrus in vitro by (S)-3,5-dihydroxyphenylglycine ((S)-DHPG)

Abstract

The direct activation of metabotropic glutamate receptors (mGluRs) by 1S,3R-aminocyclopentane dicarboxylate (1S,3R-ACPD), has previously been shown to induce a relatively fast (maximum at 10 min) and slow (90 min) onset long-term potentiation (LTP) of synaptic transmission in the hippocampus. Here we report the first evidence for a relatively fast onset LTP of synaptic transmission in the immature male rat (50–100 g) dentate gyrus in vitro by application of the mGluR type I agonist, (S)-3,5-dihydroxyphenylglycine ((S)-DHPG; 20 μM). Bath application of (S)-DHPG caused a transient depression of the field excitatory postsynaptic potential (EPSP) slope, followed after washout by a relatively rapidly developing potentiation of synaptic transmission to a maximum increase at 12–15 min (161.1±11.4% compared to controls at 15 min; n=8). This effect was not observed following perfusion with the enantiomer (R,S)-DHPG at the same dose. The (S)-DHPG potentiation occluded tetanically induced LTP and vice versa. The potentiation was antagonised by the non-specific mGluR antagonist (R,S)- α-methyl-4-carboxyphenylglycine ((R,S)-MCPG) at high doses (500–1000 μM) but was unaffected in the presence of the N-methyl- d-aspartate (NMDA) receptor blocker, d(−)-2-amino-5-phosphonopentanoic acid ( d-AP5; 50 μM). Our results demonstrate a robust NMDA-independent LTP induced by (S)-DHPG that occludes tetanically induced LTP.