Theta rhythmic stimulation of stratum lacunosum-moleculare in rat hippocampus contributes to associative LTP at a phase offset in stratum radiatum

Computational modeling demonstrates that encoding and context-dependent retrieval of memories in regionCA1 of the hippocampus will be most effective when the phase of strongest entorhinal input ( to stratum lacunosum-moleculare) is offset from the phase of maximal induction of long-term potentiation at Schaffer collateral synapses ( in s. radiatum). This would allow entorhinal input to play a role in both retrieval and encoding without engaging long-term potentiation (LTP) during retrieval. Experiments in brain slice preparations of the hippocampal formation tested the relationship between rhythmic input to s. lacunosum-moleculare and the time of maximal LTP induction at Schaffer collateral synapses in s. radiatum. Analysis of the data demonstrates a statistically significant difference in the induction of LTP for different time intervals between the end of each four-pulse train in s. lacunosum-moleculare and the single pulse s. radiatum stimulation. The time of maximal LTP induction was found to be similar to30 ms after the end of lacunosum-moleculare stimulation, consistent with the requirements of the model.