Biophysical characteristics of activity-induced sodium signals in central neurons

维持低的细胞内钠浓度是神经元产生电信号的基础。此外，它还为质膜上的多种运输过程提供能量，其中包括Na+/Ca 2+交换（NCX），其使用电化学钠梯度输出钙。最近的研究，部分由我们的实验室，表明，生理活动引起短暂的钠浓度增加树突和棘。由于钠梯度变化会产生多种功能后果，因此了解此类活动诱导的钠信号的决定因素和特征是必不可少的。本提案的主要目标是提供，第一次，定义和形状活动诱导的神经元钠瞬变的生物物理参数的详细分析。具体来说，我们的目标是确定内源性和外源性缓冲和扩散特性的钠，以及空间扩散的钠信号沿着树突和树突和棘之间使用定量宽场和高分辨率钠成像。此外，我们将研究树突棘是否将钠信号区室化，并研究神经元微区中局部钠和钙信号之间的关系。基于我们的实验结果，我们将进行动力学计算机模拟，这将提供一个定量模型的钠瞬变。因此，我们的项目将提供一个全面的了解活动诱导的钠信号在中枢神经元的时间和空间特性。

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.