Sodium Dynamics in Pyramidal Neuron Dendritic Spines: Synaptically Evoked Entry Predominantly through AMPA Receptors and Removal by Diffusion

Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties using newly developed simultaneous sodium and calcium imaging with single-spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high-speed, low-noise CCD camera. Following subthreshold electrical stimulation, postsynaptic sodium entry is almost entirely through AMPA receptors with little contribution from entry through NMDA receptors or voltage-gated sodium channels. Sodium removal from the spine head is through rapid diffusion out to the dendrite through the spine neck with a half-removal time of ~16 ms, which suggests the neck has low resistance. Peak [Na⁺]_i changes during single EPSPs are ~5 mm. Stronger electrical stimulation evoked small plateau potentials that had significant longer-lasting localized [Na⁺]_i increases mediated through NMDA receptors.

SIGNIFICANCE STATEMENT Dendritic spines, small structures that are difficult to investigate, are important elements in the fundamental processes of synaptic integration and plasticity. The main tool for examining these structures has been calcium imaging. However, the kinds of information that calcium imaging reveals is limited. We used newly developed, high-speed, simultaneous sodium and calcium imaging to examine ion dynamics in spines in hippocampal pyramidal neurons. We found that following single subthreshold synaptic activation most sodium entry was through AMPA receptors and not through NMDA receptors or through voltage-gated sodium channels and that the spine neck is not a significant resistance barrier. Most spine mechanisms are linear. However, regenerative NMDA conductances can be activated with stronger stimulation.