Priming of long-term potentiation mediated by ryanodine receptor activation in rat hippocampal slices.

Administration of the Group 1 metabotropic glutamate receptor (mGluR) agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) facilitates ("primes") subsequent long-term potentiation (LTP) through a phospholipase C signaling cascade that may involve release of Ca2+ from the endoplasmic reticulum (ER). We investigated the intracellular calcium pathways involved in this priming effect, recording field potentials from area CA1 of rat hippocampal slices before and after high-frequency stimulation. The priming of LTP by DHPG was prevented by co-administration of cyclopiazonic acid, which depletes ER Ca2+ stores. The priming effect was also blocked by the ryanodine receptor (RYR) antagonist ryanodine (RYA, 100 microM). In contrast, a low dose of RYA (10 microM) which opens the RYR channel, by itself primed LTP. In addition to RYR activation, entry of extracellular calcium through store-operated channels appears necessary for priming, since diverse treatments known to impede store-operated channel activity completely blocked both RYA and DHPG priming effects. Thus, RYR activation plays a critical role in the priming of LTP by Group 1 mGluRs, and this effect is coupled to the entry of extracellular calcium, probably through store-operated calcium channels.