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The Journal of Neuroscience, March 1, 2000, 20(5):1791-1799

NMDA Receptor-Mediated Subthreshold Ca²⁺ Signals in Spines of Hippocampal Neurons

Yury Kovalchuk^{1, 2}, Jens Eilers¹, John Lisman¹, and Arthur Konnerth^{1, 2}

¹ Physiologisches Institut, Universität des Saarlandes, 66421 Homburg, Germany, and ² Institut für Physiologie, Technische Universität München, 80802 München, Germany

We have used rapid confocal microscopy to investigate the mechanism of Ca²⁺ signals in individual dendritic spines of hippocampal CA1 pyramidal cells. The experiments focused on the signals that occur during single weak synaptic responses that were subthreshold for triggering postsynaptic action potentials. These Ca²⁺ signals were not strongly affected by blocking the EPSPs with the AMPA receptor antagonist CNQX. The signals were also not strongly reduced by blocking T-type voltage-gated Ca²⁺ channels (VGCCs) with Ni²⁺ or by blocking a broad range of VGCCs with intracellular D890. The spine Ca²⁺ signals were blocked by NMDA receptor channel (NMDAR) antagonist and had the voltage dependence characteristic of these channels. Neither ryanodine nor cyclopiazonic acid (CPA), substances known to deplete intracellular Ca²⁺ stores, substantially reduced the amplitude of synaptically evoked Ca²⁺ signals. CPA slowed the recovery phase of Ca²⁺ signals in spines produced by synaptic stimulation or by backpropagating action potentials, suggesting a role of intracellular stores in Ca²⁺ reuptake. Thus, we find that Ca²⁺ release from intracellular stores is not required to produce spine Ca²⁺ signals. We conclude that synaptic Ca²⁺ signals in spines are primarily caused by Ca²⁺ entry through NMDARs. Although these channels are largely blocked by Mg²⁺ at voltages near the resting potential, they can nevertheless produce significant Ca²⁺ elevation. The resulting Ca²⁺ signals are an integral component of individual evoked or spontaneous synaptic events and may be important in the maintenance of synaptic function.

Key words: dendritic spines; NMDA; Ca²⁺ channels; Ca²⁺ stores; subthreshold Ca²⁺ signals; hippocampus; ryanodine; CPA; confocal microscopy

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2051791-09$05.00/0

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