The Journal of Neurophysiology Vol. 85 No. 1 January 2001, pp. 399-406
Copyright ©2001 by the American Physiological Society

Bidirectional Synaptic Plasticity Correlated With the Magnitude of Dendritic Calcium Transients Above a Threshold

Department of Neurosciences, University of New Mexico, School of Medicine, Albuquerque, New Mexico 87131

Cormier, R. J., A. C. Greenwood, and J. A. Connor. Bidirectional Synaptic Plasticity Correlated With the Magnitude of Dendritic Calcium Transients Above a Threshold. J. Neurophysiol. 85: 399-406, 2001. 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 (~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 ~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 (~180 nM) and for the transition from LTD to LTP (~540 nM) may assist in constraining the molecular details of such models.