BIOPHYSICS--MODELING VELOCITY STORAGE NEURAL INTEGRATION

这项研究计划的主要目的是确定前庭-眼神经系统中速度储存神经积分器（VSNI）的生物物理和细胞基质。 现有的前庭积分器的神经模型在很大程度上依赖于经常性的正反馈网络来实现整合。然而，在金鱼和哺乳动物中识别的整合神经元中，缺乏必要的经常性轴突侧支反馈的解剖学证据。 初步分析表明，VSNI神经元表现为分数阶积分器，然而，目前在神经水平上既不了解分数阶动力学行为，也不了解积分动力学行为。 拟议的研究将开发数学，分析和方法技术，用于随后更大的研究细胞和网络属性的相对贡献速度存储神经集成。 具体目的是（1）验证金鱼VSNI神经元是分数阶积分器的假设，并量化其积分特性：（2）验证观察到的II区神经元分支几何形状和树突突起类型的异质性与观察到的反应动力学多样性之间存在因果关系的假设;（3）通过对VSNI神经元的生物病理学模拟，抽象出树突分支拓扑结构、树突不均匀性和内在膜电流对部分和整合反应动力学的贡献。预期结果是：VSNI神经元的综合反应动力学范围的表征;分形结构特性和可能的分数综合反应动力学之间的相关性，以及内在结构和细胞因素在产生这些动力学中的相对作用的估计。 本项目的独特之处在于：（1）使用金鱼标本，其中速度存储神经元易于识别，数量有限，可用于逼真的建模和结构-功能实验，包括单细胞夏普和贴片电极记录;（2）利用新的数学方法将分数积分动力学与分形树枝状结构联系起来，包括三维分形维数的计算和从物理基础导出分数阶微分方程的新分析技术。 这项研究将提供的方法和试点结果，为未来的神经基础的速度存储和角度VOR空间定位模型为基础的研究。 这些结果将影响当前前庭眼功能的系统级模型，以及神经科学多个领域中持续神经活动和短期记忆的一般理论模型。

The broad objective of this research program is to determine the biophysical and cellular substrate of the velocity storage neural integrator (VSNI) in the vestibulo-oculomotor system. Existing neural models of vestibular integrators rely largely on recurrent positive feedback networks to implement the integration. Anatomic evidence for the requisite recurrent axon collateral feedback in identified integrator neurons in goldfish and in mammals, however, is lacking. Preliminary analyses suggest that VSNI neurons behave as fractional order integrators; however, neither fractional nor integrative dynamical behaviors is presently understood at the neural level. The proposed research will develop the mathematical, analytic and methodological techniques to be used in a subsequent larger study of the relative contributions of cellular and network properties to velocity storage neural integration. The specific aims are (1) to test the hypothesis that VSNI neurons in goldfish are fractional order integrators, and quantify their integrative properties; (2) to test the hypothesis that the observed range of branching geometries and heterogeneity of dendritic process types in Area II neurons is causally related to the diversity of observed response dynamics; (3) to abstract the contributions of dendritic branching topology, dendritic nonuniformity and intrinsic membrane currents to fractional and integrative response dynamics via biophysically realistic modeling of VSNI neurons. The expected results are: characterization of the range of integrative response dynamics in VSNI neurons; correlation between fractal structural properties and possibly fractional integrative response dynamics and an estimate of the relative roles of intrinsic structural and cellular factors in producing these dynamics. The unique features of this project are (1) use of the goldfish preparation in which velocity storage neurons are easily identified, finite in number for realistic modeling and structure-function experiments that include both single cell sharp and patch electrode recordings; (2) use of new mathematical methods for relating fractional integrative dynamics to fractal dendritic structures, including computation of 3-D fractal dimension and new analytic techniques for deriving fractional differential equations from their physical substrates. This research will provide the methodology and pilot results for future model-based studies of the neural basis of velocity storage and angular VOR spatial orientation. These results will impact on current system-level models of vestibulo-ocular function, and on general theoretical models of persistent neural activity and short-term memory in multiple areas of neuroscience.