PREDICTIVE MODELING OF BIOELECTRIC ACTIVITY ON MAMMALIAN MULTILAYERED NEURONAL STRUCTURES IN THE PRESENCE OF SUPRAPHYSIOLOGICAL ELECTRIC FIELDS

项目摘要 这种多尺度建模研究的最终目标是弥合三维、全三维和三维之间存在的差距。 波、电磁生物相互作用的宏观建模（全局建模）和细胞级建模 战略布局我们的研究团队由工程师和神经科学家组成，他们是所有领域的专家。 计算和实验方面的必要，以填补现有的差距，在多尺度建模。 这项多所大学的努力是根据电流密度预测活动神经元的时空分布 通过多电极电刺激产生的细胞依赖于具有一组分子的“核心模型”， （受体通道动力学）、突触、神经元和多神经元活动。这些模型及其输入， 输出必须被整合到细胞外介质/基质的全局模型中，包括相关的多- 电极阵列在这些层面上成功的建模将允许关于时空模式的假设， 电刺激以产生关于激活输入的数量和分布的预测（基于 传入轴突的已知空间分布）。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， 因此，编码神经系统中所有信息的尖峰序列活动的时空分布。 此外，我们相信所提出的多尺度建模框架构成了一个理想的平台， 产生新的见解的致病机制沉淀异常海马功能。 虽然拟议的研究集中在海马系统，我们的努力将利用我们的 在我们最初的多尺度建模U 01的性能期间完成的多尺度建模 格兰特，在视网膜和皮质假体领域。

Project Abstract 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 and neuroscientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This 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. Further, we believe the proposed multiscale modeling framework constitutes an ideal platform capable of generating novel insights into the pathogenic mechanisms precipitating abnormal hippocampal function. Although the proposed research is focused on the hippocampal system, our effort will capitalize on our multiscale modeling accomplishments during the performance period of our original multiscale modeling U01 grant, in the realm of both retinal and cortical prostheses.