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

Sodium ions $\left({\text{Na}}^{+}\right)$ are major charge carriers mediating neuronal excitation and play a fundamental role in brain physiology. Glutamatergic synaptic activity is accompanied by large transient ${\text{Na}}^{+}$ increases, but the spatio-temporal dynamics of ${\text{Na}}^{+}$ signals and properties of ${\text{Na}}^{+}$ diffusion within dendrites are largely unknown. To address these questions, we employed multi-photon ${\text{Na}}^{+}$ 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 ${\text{Na}}^{+}$ concentration of ~10 mM. Using intensity-based line-scan imaging we found that local, glutamate-evoked ${\text{Na}}^{+}$ signals spread rapidly within dendrites, with peak amplitudes decreasing and latencies increasing with increasing distance from the site of stimulation. Spread of ${\text{Na}}^{+}$ along dendrites was independent of dendrite diameter, order or overall spine density in the ranges measured. Our experiments also show that dendritic ${\text{Na}}^{+}$ 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 ${\text{D}}_{{\text{Na}}^{+}}=600\mu {\text{m}}^2/\text{s}$ . Modeling moreover revealed that lateral diffusion is key for the clearance of local ${\text{Na}}^{+}$ increases at early time points, whereas when diffusional gradients are diminished, ${\text{Na}}^{+}/{\text{K}}^{+}$ -ATPase becomes more relevant. Taken together, our study thus demonstrates that ${\text{Na}}^{+}$ influx causes rapid lateral diffusion of ${\text{Na}}^{+}$ within spiny dendrites. This results in an efficient redistribution and fast recovery from local ${\text{Na}}^{+}$ transients which is mainly governed by concentration differences.