STDP under various external calcium concentrations. (A) t-LTP and t-LTD are induced at low frequency (0.3 Hz). The pre-post protocol is repeated 100 times, while the post-pre protocol is repeated 150 times. The action potential is induced by the injection of a depolarizing current into a CA1 neuron recorded in a whole-cell configuration. The EPSP is evoked by a stimulation electrode placed in the Schaffer collaterals. The delay (Δt) is varied according to the experiments. (B) In 3 mM extracellular calcium, a pre-post protocol (positive delays; +5 < Δt < +25 ms; red) leads to t-LTP and a post-pre (negative delays; −25 < Δt < −5 ms; green) protocol leads to t-LTD. Note the presence of a second t-LTD window at around +40/+60 ms. To facilitate comparison between the data, the duration of the negative pairing has been set to that of the positive pairing. (C) In 1.8 mM extracellular calcium, both pre-post protocols (+5 < Δt < +25 ms; red) and post-pre protocols (−25 < Δt < −5 ms; green) lead to t-LTD. The t-LTP window is absent under these conditions. (D) In 1.3 mM extracellular calcium, on average, no plasticity is induced regardless of the delay. The t-LTP and t-LTD window are missing under these conditions. (E, Left) Synaptic changes for a pre-post protocol at +10 ms. No plasticity is induced for calcium concentrations of 1.3 and 1.5 mM. For 1.8 mM calcium, t-LTD is induced, while for 2.5, and 3 mM calcium, t-LTP is induced. (E, Right) Synaptic changes for a post-pre protocol at −25 ms. No plasticity is induced in 1.3 and 1.5 mM calcium. For 1.8, 2.5, and 3 mM calcium, t-LTD is induced. Note the difference between the results in the range of physiological calcium concentration (green squares) and the results in nonphysiological calcium concentration.