Altered spike timing-dependent plasticity rules in physiological calcium

Like many forms of long-term synaptic plasticity, spike-timing-dependent plasticity (STDP) depends on intracellular Ca2+ signaling for its induction. Yet, all in vitro studies devoted to STDP used abnormally high external Ca2+ concentration. We measured STDP at the CA3-CA1 hippocampal synapses under different extracellular Ca2+ concentrations and found that the sign, shape and magnitude of plasticity strongly depend on Ca2+. A pre-post protocol that results in robust LTP in high Ca2+, yielded only LTD or no plasticity in the physiological Ca2+ range. LTP could be restored by either increasing the number of post-synaptic spikes or increasing the pairing frequency. A calcium-based plasticity model in which depression and potentiation depend on post-synaptic Ca2+ transients was found to fit quantitatively all the data, provided NMDA receptor-mediated non-linearities were implemented. In conclusion, STDP rule is profoundly altered in physiological Ca2+ but specific activity regimes restore a classical STDP profile.