Activation of group I metabotropic glutamate receptors induces long-term depression in the hippocampal CA1 region of adult rats in vitro.

Previous studies have implicated that long-term depression (LTD) was developmentally regulated since LTD can be readily induced by low frequency stimulation (LFS) in acute hippocampal slices prepared from juvenile but not adult animals. Here, we have examined the LTD induced by LFS (1Hz, 900 pulses) paired with a certain pattern at the Schaffer collateral-CAl synapse in adult hippocampal slices. We found that, in the 90-day-old rat hippocampus, LTD could be induced reliably by LFS paired with stronger stimulus intensity than that used during baseline recording. However, this synaptic depression could be completely abolished by application of metabotropic glutamate receptor (mGluR) antagonist (S)-amethyl-4-carboxyphenylglycine (MCPG) which had no effect on that induced by the same protocol in the 16-day-old rat hippocampus. Furthermore, preincubation with group I mGluR antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and (S)-2-methyl-4-carboxyphenylglycine (LY367385), also completely prevented the LFS-induced LTD. In contrast, group II mGluR antagonist (2S)-a-ethylglutamic acid (EGLU), N-methyl-d-aspartate (NMDA) receptor antagonist APV and voltage-gated calcium channel antagonist nimodipine had no effect on the LFS-induced LTD. Taken together, these observations suggest that LFS paired with strong stimulus strength can efficiently induce group I mGluR-dependent LTD in the adult hippocampal CA1 region, proving insight into the functional significance of hippocampal mGluR-mediated LTD in learning and memory.