Extracellular calcium modulates persistent sodium current-dependent burst-firing in hippocampal pyramidal neurons

The generation of high-frequency spike bursts ("complex spikes"), either sp ontaneously or in response to depolarizing stimuli applied to the soma, is a notable feature in intracellular recordings from hippocampal CA1 pyramida l cells (PCs) in vivo. There is compelling evidence that the bursts are int rinsically generated by summation of large spike afterdepolarizations (ADPs ). Using intracellular recordings in adult rat hippocampal slices, we show that intrinsic burst-firing in CA1 PCs is strongly dependent on the extrace llular concentration of Ca2+ ([Ca2+](o)). Thus, lowering [Ca2+](o) (by equi molar substitution with Mn2+ or Mg2+) induced intrinsic bursting in nonburs ters, whereas raising [Ca2+](o) suppressed intrinsic bursting in native bur sters. The induction of intrinsic bursting by low [Ca2+](o) was associated with enlargement of the spike ADP. Low [Ca2+](o)-induced intrinsic bursts a nd their underlying ADPs were suppressed by drugs that reduce the persisten t Na+ current (I-NaP), indicating that this current mediates the slow burst depolarization. Blocking Ca2+- activated K+ currents with extracellular Ni 2+ or intracellular chelation of Ca2+ did not induce intrinsic bursting. Th is and other evidence suggest that lowering [Ca2+](o) may induce intrinsic bursting by augmenting I-NaP. Because repetitive neuronal activity in the h ippocampus is associated with marked decreases in [Ca2+](o), the regulation of intrinsic bursting by extracellular Ca2+ may provide a mechanism for pr eferential recruitment of this firing mode during certain forms of hippocam pal activation.