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 µm 2 /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.