Sustained dendritic gradients of Ca²⁺ induced by excitatory amino acids in CA1 hippocampal neurons

Spatially resolved measurements of intracellular free calcium and of the changes produced by excitatory amino acids were made in neurons isolated from adult mammalian brain. Extremely long-lasting (minutes) Ca²⁺ gradients were induced in the apical dendrites of hippocampal CA1 neurons after brief (1 to 3 seconds), local application of either glutamate or N-methyl-D-aspartate (NMDA). These gradients reflect the continuous flux of Ca²⁺ into the dendrite. The sustained gradients, but not the immediate transient response to the agonists, were prevented by prior treatment with the protein kinase C inhibitor sphingosine. Expression of the long-lasting Ca²⁺ gradients generally required a priming or conditioning stimulus with the excitatory agonist. The findings demonstrate a coupling between NMDA receptor activation and long-lasting intracellular Ca²⁺ elevation that could contribute to certain use-dependent modifications of synaptic responses in hippocampal CA1 neurons.