Predictive modeling of bioelectric activity on mammalian multilayered neuronal st

描述（由申请人提供）：这项多尺度建模研究的最终目标是弥合三维，全波，宏观电和磁生物相互作用建模（全局建模）和细胞水平建模策略之间存在的差距。我们的研究团队由工程师、神经科学家、生物物理学家、外科医生和计算机科学家组成，他们是填补多尺度建模现有空白所必需的所有计算和实验方面的专家。这项由多所大学联合开展的新研究，基于多电极电刺激产生的电流密度来预测活跃神经元的时空分布，这取决于一套分子（受体通道动力学）、突触、神经元和多神经元活动的“核心模型”。这些模型及其输入和输出必须集成到细胞外介质/基质的全局模型中，包括相关的多电极阵列。在这些层面上的成功建模将允许假设电刺激的时空模式，从而产生关于激活输入的数量和分布的预测（基于已知的传入轴突的空间分布）。连接的分子，突触，神经元，多神经元和全局模型将为活跃神经元的时空分布的新兴预测提供基础，从而为编码神经系统中所有信息的尖峰序列活动的时空分布提供基础。我们的研究工作

DESCRIPTION (provided by applicant): The end goal of this multiscale modeling research is to bridge the gap existing between three-dimensional, full- wave, macro-modeling of electrical and magnetic biointeractions (global modeling) and cellular-level modeling strategies. Our research team is composed of engineers, neuroscientists, biophysicists, surgeons, and computer scientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This new multi-university effort to predict spatio-temporal distributions of active neurons based on current densities created by multi-electrode electrical stimulation depends on having a set of "core models" of molecular (receptor-channel kinetics), synaptic, neuron, and multi-neuron activity. These models and their inputs and outputs must be integrated into a global model of the extracellular media/matrix including relevant multi-electrode arrays. Successful modeling at these levels will allow hypotheses about space-time patterns of electrical stimulation to produce predictions about the number and distribution of activated inputs (based on known spatial distributions of afferent axons). The linked molecular, synaptic, neuron, multi-neuron, and global model will provide the basis for emerging predictions of the spatio-temporal distribution of active neurons and thus, the spatio-temporal distributions of spike train activity that encode all information in the nervous system. Our research effort will capitalize on our accomplishments in the realm of retinal and cortical prostheses, and use these as test beds for the multiscale predictive modeling methods that we will develop within the proposed activity. PUBLIC HEALTH RELEVANCE: The relevance of this research to the public health consists of the development of a generalizable engineering approach to the optimization of existing and proposed neural interfaces, which will produce enormous benefit to the neurologically disabled. We expect that the results of this work will profoundly affect the way we design neurostimulating electrodes and provide a deep understanding of the optimal shape and size of electrodes, waveform characteristics and timing differences between stimulating currents in adjacent electrodes, and current levels to name a few.