Induction of synaptic depression by high-frequency stimulation in area CA1 of the rat hippocampus: Modeling and experimental studies

It is generally accepted that low-frequency stimulation (LFS) induces long-term depression (LTD), while high-frequency stimulation (HFS) induces long-term potentiation (LTP). We performed modeling and experimental studies to see whether this commonly accepted view is the case for a wide range of stimulation frequencies, and found the induction of LTD by high-frequency stimulation of 300 Hz (HFS-LTD) both in simulation and experiments. HFS-LTD was occluded by standard LFS-LTD induced by 1 Hz–15 min stimulation, and blocked by D-AP5, W-7 or FK-506, but neither by Ni+ nor nimodipine. The analysis of the model suggested that the crossing of activation curve of CaMKII twice with that of CaN as the increase in [Ca2+]i was a possible mechanism for the induction of HFS-LTD in our study.