An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat

1. We have investigated the prediction of a relationship between the magnit ude of activity dependent increases in postsynaptic calcium and both the ma gnitude and direction of synaptic plastic change in the central nervous sys tem. Activity-dependent increases in calcium were buffered to differing deg rees using a range of concentrations of EGTA and the effects on synaptic pl asticity were assessed. 2. Activity-dependent synaptic plasticity was induced during whole-cell rec ording in rat perirhinal cortex in vitro. In control conditions (0.5 mM EG- TB) low frequency stimulation (LFS; 200 stimuli) delivered to neurones held at -40 or -70 mV induced long-term depression (LTD) or, at -10 mV, induced long-term potentiation (LTP). 3. The relationship between EGTA concentration (0.2 to 10 mM) and the magni tude of LTD was examined. This relationship described a U-shaped curve, as predicted by models of synaptic plasticity. This provides strong evidence t hat the magnitude of LTD is determined by the magnitude of the increase in intracellular calcium concentration. 4. LFX paired with depolarisation to -10 mV induced LTD, no change or LTP a s activity dependent postsynaptic calcium levels were allowed to increase p rogressively by the use of progressively lower concentrations of buffer (10 to 0.2 mar EGTA). 5. We investigated if the lack of plasticity that occurs at the transition between LTD and LTP is due to induction of both of these processes with zer o net change, or is due to neither LTD nor LTP being induced. These experim ents were possible as LTP but not LTD was blocked by the protein kinase inh ibitor staurosporine while LTD but not LTP was blocked by the mGlu receptor antagonist MCPG. Bt the transition between LTD and LTP, blocking LTP mecha nisms did not uncover LTD whilst blocking LTD mechanisms did not uncover LT P. This suggests that the transition between LTD and LTP is due to the lack of induction of both of these processes and also suggests that these two p rocesses are induced independently of one another.