Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold

The magnitude of postsynaptic Ca2+ transients is thought to affect activity-dependent synaptic plasticity associated with learning and memory. Large Ca2+ transients have been implicated in the induction of long-term potentiation (LTP), while smaller Ca2+ transients have been associated with long-term depression (LTD). However, a direct relationship has not been demonstrated between Ca2+ measurements and direction of synaptic plasticity in the same cells, using one induction protocol. Here, we used glutamate iontophoresis to induce Ca2+ transients in hippocampal CA1 neurons injected with the Ca2+- indicator fura-2. Test stimulation of one or two synaptic pathways before and after iontophoresis showed that the direction of synaptic plasticity correlated with glutamate-induced Ca2+ levels above a threshold, below which no plasticity occurred (similar to 180 nM). Relatively low Ca2+ levels (180-500 nM) typically led to LTD of synaptic transmission and higher levels (>500 nM) often led to LTP. Failure to show plasticity correlated with Ca2+ levels in two distinct ranges: <180 nM and <similar to>450-600 nM, while only LTD occurred between these ranges. Our data support a class of models in which failure of Ca2+ transients to affect transmission may arise either from insufficient Ca2+ to affect Ca2+-sensitive proteins regulating synaptic strength through opposing activities or from higher Ca2+ levels that reset activities of such proteins without affecting the net balance of activities. Our estimates of the threshold Ca2+ level for LTD (similar to 180 nM) and for the transition from LTD to LTP (similar to 540 nM) may assist in constraining the molecular details of such models.