INTRACELLULAR CA2-COURSE OF LTP INDUCTION - A MODEL OF CA2+ DYNAMICS IN DENDRITIC SPINES( STORES CAN ACCOUNT FOR THE TIME)

1. A model of Ca2+ dynamics in spines of CA1 hippocampal neurons is pr esented. In contrast to traditional models, which concentrate on the e ffects of Ca2+ influx, diffusion, buffering, and extrusion, we also co nsider the additional effect of intracellular Ca2+ stores. 2. It is sh own that traditional models without Ca2+ stores cannot account for the time course of long-term potentiation (LTP) induction as found in rec ent experiments. Experimental data suggest that the intracellular Ca2 concentration should be elevated for up to 2 s, whereas the Ca2+ conc entration in standard models of Ca2+ dynamics decays much faster. 3. W hen intracellular Ca2+ stores are taken into account, a much slower de cay is found. In particular, a model simulation with a stimulation par adigm consisting of two bursts of four impulses at 100 Hz each and var iable interburst intervals can reproduce experimental results found fo r primed or theta-burst stimulation. 4. In our model, Ca2+ release fro m the store has a nonlinear, bell-shaped dependence on the intracellul ar Ca2+ concentration, similar to the one found for inositoltrisphosph ate and ryanodine receptors. These receptors are known to control calc ium release from intracellular stores. 5. Our model suggests an import ant role of intracellular calcium stores in the induction of LTP. The stores serve as a long-term calcium source that can sustain an intrace llular Ca2+ concentration above the resting level for 1-2 s.