Integrated Biophysical and Neural Model of Electrical Stimulation Effects

项目摘要 电刺激被广泛用于激活和/或破坏神经元的活动。尽管它很关键 在实验和临床神经科学中的重要性，目前还没有经过验证的方法来预测 大脑中的哪些神经元素会被给定的刺激机制激活。根据我们的飞行员 研究中，我们建议开发一种新的计算方法来预测特定的神经元 它将被给定的刺激方案激活，基于神经元的形状、位置、类型和 连通性。我们将使用生物物理模型来计算激活电流的空间分布， 然后将这种分布与轴突和树突的空间分布和方向进行卷积 主要的锥体细胞和中间神经元细胞类型，以确定它们的放电概率。到时候我们会的 通过大脑皮层回路传播这种活动。我们将模拟不同的物种(大鼠、小鼠、人类) 和大脑皮层区域(初级感觉和联想)。我们将研究睡眠阶段和 诱发的丘脑皮质网络的背景活动，包括特有的睡眠节律 活动。模型的预测将通过广泛的经验测量进行验证，主要是 使用先进的显微镜方法对小鼠进行钙成像，使整个相关的大脑皮层 要以高分辨率表征的体积。细胞类型特异性标记和解剖重建 将允许识别不同的神经元群体并测量它们的激活概率。 这将由电压敏感染料成像和层流电生理记录来补充，以 提供时间分辨率。层流记录将在人类身上重复，在两种急性 术中和半慢性环境。将根据验证研究对模型进行修改。这个 集成的生物物理和神经模型以及文档和教程将在 网络。

Project Abstract Electrical stimulation is widely used to activate and/or disrupt neuronal activity. Despite its critical importance in experimental and clinical neuroscience, at present, there is no validated method to predict which neural elements of the brain will be activated by a given stimulation regime. Based on our pilot studies, we propose here to develop a novel computational approach for predicting the specific neurons which will be activated by a given stimulation protocol, based on neuron shape, location, type and connectivity. We will use biophysical modeling to calculate the spatial distribution of activating currents, and then convolve this distribution with the spatial distribution and orientation of the axons and dendrites of the major pyramidal and interneuron cell types to determine their probability of firing. We will then propagate this activity through the cortical circuitry. We will model different species (rats, mice, humans) and cortical areas (primary sensory and associative). We will examine the effects of sleep stage and background activity, including characteristic sleep rhythms, on the evoked thalamocortical network activity. The predictions of the model will be validated with extensive empirical measurements, primarily calcium imaging in mice using advanced microscopy methods that allow the entire relevant cortical volume to be characterized at high resolution. Cell type specific labeling and anatomical reconstructions will permit identification of different neuronal populations and measurement of their activation probability. This will be supplemented by voltage-sensitive dye imaging and laminar electrophysiological recordings to provide temporal resolution. The laminar recordings will be repeated in humans, in both acute intraoperative and semi-chronic settings. The models will be modified in light of the validation studies. The integrated biophysical and neural model with documentation and tutorials will be made available on the web.