Fast Synaptically Activated Calcium and Sodium Kinetics in Hippocampal Pyramidal Neuron Dendritic Spines.

An accurate assessment of the time course, components, and magnitude of postsynaptic currents is important for a quantitative understanding of synaptic integration and signaling in dendritic spines. These parameters have been studied in some detail in previous experiments, primarily using two-photon imaging of [Ca] changes and two-photon uncaging of glutamate. However, even with these revolutionary techniques, there are some missing pieces in our current understanding, particularly related to the time courses of synaptically evoked [Ca] and [Na] changes. In new experiments, we used low-affinity, linear Na and Ca indicators, laser fluorescence stimulation, and a sensitive camera-based detection system, combined with electrical stimulation and two-photon glutamate uncaging, to extend measurements of these spine parameters. We found that (1) almost all synaptically activated Na currents in CA1 hippocampal pyramidal neuron spines in slices from mice of either sex are through AMPA receptors with little Na entry through voltage-gated sodium channels (VGSCs) or NMDA receptor channels; (2) a spectrum of sodium transient decay times was observed, suggesting a spectrum of spine neck resistances, even on the same dendrite; (3) synaptically activated [Ca] changes are very fast and are almost entirely because of Ca entry through NMDA receptors at the time when the Mg block is relieved by the fast AMPA-mediated EPSP; (4) the [Ca] changes evoked by uncaging glutamate are slower than the changes evoked by synaptic release, suggesting that the relative contribution of Ca entering through NMDA receptors at rest following uncaging is higher than following electrical stimulation.