Long-term plasticity in cingulate cortex requires both NMDA and metabotropic glutamate receptor activation.

We tested whether induction of homosynaptic long-term potentiation and long-term depression of synaptic strength in posterior cingulate cortex requires NMDA and/or metabotropic glutamate (mGlu) receptor activation. In in-vitro slices of rat posterior cingulate cortex, the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (D-AP5; 15-20 microM) blocked induction of both long-term potentiation and long-term depression of mono- and polysynaptic population potentials in deep laminae. In contrast, DL-2-amino-3-phosphonopropionic acid (DL-AP3; 15-25 microM), a selective mGlu receptor antagonist, blocked homosynaptic long-term potentiation and long-term depression of monosynaptic transmission, but was ineffective in blocking the induction of either type of plasticity at polysynaptically-driven sites. The selective mGlu receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), induced a marked depression of subicular-evoked monosynaptic potentials which reversed upon drug washout, but produced little depression of polysynaptic responses. We conclude that metabotropic glutamate receptor activation is necessary for the induction of long-term synaptic plasticity only at monosynaptic subiculo-cingulate terminals, while NMDA receptor activation is necessary for the induction of long-term potentiation/long-term depression of both mono- and polysynaptic pathways.