Coactivation of Local Circuit NMDA Receptor Mediated epsps Induces Lasting Enhancement of Minimal Schaffer Collateral epsps in Slices of Rat Hippocampus

Lasting enhancement of minimal Schaffer collateral epsps in CA1 pyramidal neurons was induced when these epsps were coactivated with putative local circuit N‐methyl‐d‐aspartate (NMDA) receptor‐mediated epsps. In transverse slices of hippocampus, minimal epsps were evoked by stimulating the Schaffer collateral/commissural pathway within CA3 stratum radiatum and the local circuit axons were stimulated within CA1 stratum oriens or alveus using fine, two barrel glass micropipettes. Minimal Schaffer collateral epsps were insensitive to d‐2‐amino‐5‐phosphonovalerate (AP‐5) and displayed conventional voltage relations. Local epsps were sensitive to AP‐5 and increased in amplitude and duration with membrane depolarization. High frequency tetanic stimulation of the minimal Schaffer collateral epsps induced no lasting enhancement. However, pairing of the Schaffer epsp with a frequency potentiated local epsp resulted in a delayed, but lasting increase in the Schaffer epsp. When the local epsp did not exhibit frequency potentiation during pairing, no enhancement resulted. When either epsp was contaminated with an ipsp, no lasting increase resulted. When transmission through the alveus was blocked by focal application of local anaesthetic, traditional protocols for long‐term potentiation (LTP) induction were relatively ineffective. These results indicate that a significant source of the NMDA receptor activation required for the induction of LTP in the Schaffer collateral input to CA1 derives from local circuit connections between CA1 pyramidal neurons and, moreover, that lasting enhancement can be induced with low frequency activation, at postsynaptic resting potential, in the presence of Mg2+ and with local inhibition intact.