2-Amino-3-phosphonopropionic acid, an inhibitor of glutamate-stimulated phosphoinositide turnover, blocks induction of homosynaptic long-term depression, but not potentiation, in rat hippocampus.

Recently, we have reported an associative long-term depression (LTD) of synaptic strength in hippocampal field CA1 that is produced when a low-frequency test input is negatively correlated in time with a high-frequency conditioning input. We have also found that pairing of synaptic activity with postsynaptic hyperpolarization is sufficient to induce LTD. We report here that 2-amino-3-phosphonopropionate (AP3), a selective inhibitor of phosphoinositide (PI) turnover mediated by the metabotropic glutamate receptor, blocks the induction of associative LTD in hippocampal field CA1, but does not impair the induction of LTP. Our data suggest that metabotropic glutamate receptor activation is involved in the induction of LTD.