Synaptically activated Ca2+ waves and NMDA spikes locally suppress voltage-dependent Ca2+ signalling in rat pyramidal cell dendrites.

Postsynaptic Ca(2+) changes contribute to several kinds of plasticity in pyramidal neurons. We examined the effects of synaptically activated Ca(2+) waves and NMDA spikes on subsequent Ca(2+) signalling in CA1 pyramidal cell dendrites in hippocampal slices. Tetanic synaptic stimulation evoked a localized Ca(2+) wave in the primary apical dendrites. The Ca(2+) increase from a backpropagating action potential (bAP) or subthreshold depolarization was reduced if it was generated immediately after the wave. The suppression had a recovery time of 30-60 s. The suppression only occurred where the wave was generated and was not due to a change in bAP amplitude or shape. The suppression also could be generated by Ca(2+) waves evoked by uncaging IP(3), showing that other signalling pathways activated by the synaptic tetanus were not required. The suppression was proportional to the amplitude of the Ca(2+) change of the Ca(2+) wave and was not blocked by a spectrum of kinase or phosphatase inhibitors, consistent with suppression due to Ca(2+)-dependent inactivation of Ca(2+) channels. The waves also reduced the frequency and amplitude of spontaneous, localized Ca(2+) release events in the dendrites by a different mechanism, probably by depleting the stores at the site of wave generation. The same synaptic tetanus often evoked NMDA spike-mediated Ca(2+) increases in the oblique dendrites where Ca(2+) waves do not propagate. These NMDA spikes suppressed the Ca(2+) increase caused by bAPs in those regions. Ca(2+) increases by Ca(2+) entry through voltage-gated Ca(2+) channels also suppressed the Ca(2+) increases from subsequent bAPs in regions where the voltage-gated Ca(2+) increases were largest, showing that all ways of raising Ca(2+) could cause suppression.