A MODEL FOR DENDRITIC CA2+ ACCUMULATION IN HIPPOCAMPAL PYRAMIDAL NEURONS BASED ON FLUORESCENCE IMAGING MEASUREMENTS

1. High-speed fluorescence imaging was used to measure intracellular C a2+ concentration ([Ca2+](i)) changes in hippocampal neurons injected with the Ca2+-sensitive indicator fura-2 during intrasomatic and synap tic stimulation. The results of these experiments were used to constru ct a biophysical model of [Ca2+](i) dynamics in hippocampal neurons. 2 . A compartmental model of a pyramidal neuron was constructed incorpor ating published passive membrane properties of these cells, three type s of voltage-gated Ca2+ channels characterized from adult hippocampal neurons, voltage-gated Na+ and K+ currents, and mechanisms for Ca2+ bu ffering and extrusion. 3. In hippocampal pyramidal neurons imaging of Na+ entry during electrical activity suggests that Na+ channels, at le ast in sufficient density to sustain action potentials, are localized in the soma and the proximal part of the apical dendritic tree. The mo del, which incorporates this distribution, demonstrates that action po tentials attenuate steeply in passive distal dendritic compartments or distal dendritic compartments containing Ca2+ and K+ channels. This a ttenuation was affected by intracellular resistivity but not membrane resistivity. 4. Consistent with fluorescence imaging experiments, a no nuniform distribution of Ca2+ accumulation was generated by Ca2+ entry through voltage-gated Ca2+ channels opened by decrementally propagati ng Na+ action potentials. Consequently, the largest increases in [Ca2](i) were produced in the proximal dendrites. Distal voltage-gated Ca2 + currents were activated by broad, almost isopotential action potenti als produced by reducing the overall density of K+ channels. 5. Simula tions of subthreshold synaptic stimulation produced dendritic Ca2+ ent ry by the activation of voltage-gated Ca2+ channels. In the model thes e Ca2+ signals were localized near the site of synaptic input because of the attenuation of synaptic potentials with distance from the site of origin and the steep voltage-dependence of Ca2+ channel activation. 6. These simulations support the hypotheses generated from experiment al evidence regarding the differential distribution of voltage-gated C a2+ and Na+ channels in hippocampal neurons and the resulting voltage- gated Ca2+ accumulation from action and synaptic potentials.