Spatio-temporal dynamics of lateral Na⁺ diffusion in apical dendrites of mouse CA1 pyramidal neurons

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 spatio-temporal dynamics of Na + signals and properties of Na + diffusion within dendrites are largely unknown. To address these questions, we employed multi-photon 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 . 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. Significance statement Activity of excitatory glutamatergic synapses generates large Na + transients in postsynaptic cells. Na + influx is a main driver of energy consumption and modulates cellular properties by modulating Na + -dependent transporters. Knowing the spatio-temporal dynamics of dendritic Na + signals is thus critical for understanding neuronal function. To study propagation of Na + signals within spiny dendrites, we performed fast Na + imaging combined with mathematical simulations. Our data shows that normal diffusion, based on a diffusion coefficient of 600 µm 2 /s, is crucial for fast clearance of local Na + transients in dendrites, whereas Na + export by the Na + /K + -ATPase becomes more relevant at later time points. This fast diffusive spread of Na + will reduce the local metabolic burden imposed by synaptic Na + influx.