Spatiotemporal Dynamics of Lateral Na+ Diffusion in Apical Dendrites of Mouse CA1 Pyramidal Neurons

Abstract

Sodium ions (Na⁺) are major charge carriers mediating neuronal excitation and play a fundamental role in brain physiology. Glutamatergic synaptic activity is accompanied by large transient Na⁺ increases, but the spatiotemporal dynamics of Na⁺ signals and properties of Na⁺ diffusion within dendrites are largely unknown. To address these questions, we employed multiphoton Na⁺ imaging combined with whole-cell patch clamp in dendrites of CA1 pyramidal neurons in tissue slices from mice of both sexes. Fluorescence lifetime microscopy revealed a dendritic baseline Na⁺ concentration of ∼10 mM. Using intensity-based line scan imaging, we found that local, glutamate-evoked Na⁺ signals spread rapidly within dendrites, with peak amplitudes decreasing and latencies increasing with increasing distance from the site of stimulation. Spread of Na⁺ along dendrites was independent of dendrite diameter, order, or overall spine density in the ranges measured. Our experiments also show that dendritic Na⁺ readily invades spines and suggest that spine necks may represent a partial diffusion barrier. Experimental data were well reproduced by mathematical simulations assuming normal diffusion with a diffusion coefficient of D _Na+ = 600 µm²/s. Modeling moreover revealed that lateral diffusion is key for the clearance of local Na⁺ increases at early time points, whereas when diffusional gradients are diminished, Na⁺/K⁺-ATPase becomes more relevant. Taken together, our study thus demonstrates that Na⁺ influx causes rapid lateral diffusion of Na⁺ within spiny dendrites. This results in an efficient redistribution and fast recovery from local Na⁺ transients which is mainly governed by concentration differences.

Keywords: FLIM; NKA; dendrite; glutamate; imaging; sodium.