METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION INDUCES CALCIUM WAVES WITHIN HIPPOCAMPAL DENDRITES

1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+](i)) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+](i) were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [Ca2+](i) were visualized as changes in the fluorescence of the Ca2+-sensitive dye Fluo-3. 2. Brief application of the specific mGlu receptor agonist (1S,3R)-ACPD to either the apical or basal dendrites produced initially localized increases in [Ca2+](i) that subsequently propagated as waves throughout much of the neuron. These Ca2+ waves, which propagated at similar to 40 mu m/s, were shown not to reflect intracellular Ca2+ diffusion or extracellular diffusion of ACPD and were always accompanied by small outward membrane currents. 3. Repetitive application of ACPD failed to trigger further Ca2+ release. We found that a threshold level of voltage-gated Ca2+ entry during trains of action potentials was needed to prime further mGlu-stimulated Ca2+ release. In contrast, the passage of time alone did not cause the mGlu-release system to reactivate-restoration of ACPD-stimulated Ca2+ release. The spike-mediated Ca2+ signal was unaffected by mGlu-stimulated depletion of intracellular stores. 4. These experiments demonstrate that specific mGlu receptor activation can mobilize Ca2+ in dendrites of CA1 neurons and trigger waves of Ca2+-induced Ca2+-release throughout the cell. A use-dependent relationship between voltage-gated Ca2+ entry during trains of action potentials and mGlu-stimulated Ca2+ release is suggested.