Biophysical characteristics of activity-induced sodium signals in central neurons

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The maintenance of a low intracellular sodium concentration is a basis for the generation of electrical signaling by neurons. In addition, it provides the energy for a multitude of transport processes at the plasma membrane, among them Na+/Ca2+-exchange (NCX), which uses the electrochemical sodium gradient for the export of calcium. Recent studies, in part by our laboratory, show that physiological activity evokes transient increases in the sodium concentration in dendrites and spines. Because of the manifold functional consequences of changes in the sodium gradient, understanding of the determinants and the characteristics of such activity-induced sodium signals is indispensable. The major goal of the present proposal is to provide, for the first time, a detailed analysis of the biophysical parameters which define and shape activity-induced neuronal sodium transients. Specifically, we aim to determine endo- and exogenous buffering and diffusion properties of sodium as well as the spatial spread of sodium signals along dendrites and between dendrites and spines using quantitative wide-field and high-resolution sodium imaging. Furthermore, we will investigate if dendritic spines compartmentalize sodium signals and study the relationship between local sodium and calcium signaling in neuronal microdomains. Based on our experimental results, we will perform kinetic computer simulations which will provide a quantitative model of sodium transients. Thus, our project will provide a comprehensive understanding of the temporal and spatial properties of activity-induced sodium signals in central neurons.