TY - JOUR T1 - Fast synaptically activated calcium and sodium kinetics in hippocampal pyramidal neuron dendritic spines JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0396-22.2022 SP - ENEURO.0396-22.2022 AU - Kenichi Miyazaki AU - William N. Ross Y1 - 2022/11/15 UR - http://www.eneuro.org/content/early/2022/11/14/ENEURO.0396-22.2022.abstract N2 - 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 2-photon imaging of [Ca2+]i changes and 2-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 [Ca2+]i and [Na+]i changes. In new experiments we used low affinity, linear Na+ and Ca2+ indicators, laser fluorescence stimulation, and a sensitive camera-based detection system, combined with electrical stimulation and 2-photon glutamate uncaging, to extend measurements of these spine parameters. We found that (a) 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 or NMDA receptor channels; (b) a spectrum of sodium transient decay times was observed, suggesting a spectrum of spine neck resistances, even on the same dendrite; (c) synaptically activated [Ca2+]i changes are very fast, and are almost entirely due to Ca2+ entry through NMDA receptors at the time when the Mg2+ block is relieved by the fast AMPA mediated EPSP; (d) the [Ca2+]i changes evoked by uncaging glutamate are slower than the changes evoked by synaptic release, suggesting that the relative contribution of Ca2+ entering through NMDA receptors at rest following uncaging is higher than following electrical stimulation.SignificanceDendritic spines are the main sites where synaptically activated EPSPs are initiated and calcium changes are generated. Knowledge of these signals is critical for understanding synaptic integration and plasticity We measured these changes in spines using high speed fluorescence imaging with non-buffering indicators following electrical stimulation. We found that sodium changes were primarily through AMPA receptors in spines and decayed by diffusion into dendrites with heterogenous times reflecting heterogeneous spine neck resistances. Calcium changes were fast and were primarily due to calcium entry through NMDA receptors opened when the magnesium block was relieved by the AMPA receptor mediated EPSP. We found differences between calcium signals evoked synaptically and signals evoked by 2-photon glutamate uncaging, suggesting caution in interpreting these transients. ER -