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

Abstract

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