THE SPREAD OF NA+ SPIKES DETERMINES THE PATTERN OF DENDRITIC CA2+ ENTRY INTO HIPPOCAMPAL-NEURONS

THE dendrites of many types of neurons contain voltage-dependent Na+ and Ca2+ conductances that generate action potentials (see ref. 1 for review). The function of these spikes is not well understood, but the Ca2+ entry stimulated by spikes probably affects Ca2+-dependent processes in dendrites. These include synaptic plasticity 2,3, cytotoxicity 4 and exocytosis 5. Several lines of evidence suggest that dendritic spikes occur within subregions of the dendrites 6-8. To study the mechanism that govern the spread of spikes in the dendrites of hippocampal pyramidal cells, we imaged Ca2+ entry with Fura-2 (ref. 9) and Na+ entry with a newly developed Na+-sensitive dye 10). Our results indicate that Ca2+ entry into dendrites is triggered by Na+ spikes that actively invade the dendrites. The restricted spatial distribution of Ca2+ entry seems to depend on the spread of Na+ spikes in the dendrites, rather than on a limited distribution of Ca2+ channels. In addition, we have observed an activity-dependent process that modulates the invasion of spikes into the dendrites and progressively restricts Ca2+ entry to more proximal dendritic regions.