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Creators/Authors contains: "Kafitz, Karl W"

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  1. 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 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 statementActivity 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 µm2/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. 
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    Free, publicly-accessible full text available August 6, 2026