Long-term depression in rat visual cortex is associated with a lower rise of postsynaptic calcium than long-term potentiation

To test the hypothesis that an input-associated rise of Ca2+ at postsynaptic sites beyond a certain threshold leads to the induction of long-term potentiation (LTP) while a lower rise below the threshold leads to long-term depression (LTD), the method of microscopic Ca2+ fluorometry was employed simultaneously with recordings of synaptic activity from layer II/III of visual cortical slices prepared from young rats. The conventional Ca2+ indicators, such as fura-2 or fluo-3, may interfere with intracellular processes for the induction of LTP/LTD because of their strong Ca2+-chelating action. To minimize such a problem, another Ca2+ indicator, rhod-2, was used since it has a much weaker Ca2+-chelating action than those indicators. In 16 slices loaded with rhod-2 through the perfusion medium, tetanic stimulation of theta-burst type was applied to layer IV of the cortex and changes in Ca2+ concentration were analyzed in layer II/III from which field potentials to test stimulation of layer IV were recorded simultaneously. In 7 slices in which weak tetanic stimulation consisting of 0.1 ms duration pulses was applied to layer IV, LTD of field responses was induced, while LTP was induced in 6 of the 9 slices in which strong tetanus consisting of 0.2 ms pulses was applied. In the 6 slices in which LTP was induced, the peak rise of fluorescence intensity during tetanus was 13.9 +/- 0.2 (S.E.M.) %, which was significantly (t-test, P < 0.01) higher than that (10.4 +/- 0.3%) in the 9 slices in which LTD was induced. In another series of experiments, rhod-2 was injected directly into 12 pyramidal cell-like neurons in layer II/III through patch pipettes, and changes in Ca2+ concentration in apical dendritic areas during tetanus were measured simultaneously with recordings of excitatory postsynaptic potentials (EPSPs) evoked by test stimulation of layer IV. It was found that LTP of EPSPs was induced in 4 cells which exhibited a strong rise of dendritic Ca2+ signal (197.1 +/- 18.5%) while LTD was induced in other 5 cells which showed a weak rise of the signal (31.0 +/- 4.1%). These results seem consistent with the above-mentioned, Ca2+-switching hypothesis for the induction of LTP and LTD in visual cortex.