Project 5: Computational

摘要 我们将使用详细的生物物理(动态系统)建模来探讨两个关键问题 整合和理解项目1-4的结果。大脑的生理起源是什么？ 在项目1-4中经验性研究的节奏？网络水平的节律如何取决于生理 潜在的神经元群的特性？建模使用微分方程式描述 单细胞、突触和网络水平的生理学。来自项目2和4的数据，以及之前的 模型和体外发现，将有助于建立和完善生理上可信的细胞电路模型 产生振荡。模型将有助于研究局部大脑节律、周期性(和非周期性)感觉 输入和自上而下的信号结合在一起构成主动传感。我们将严格测试有关 神经元种群、互连和细胞过程(例如，电导) 在主动感觉任务中，大脑多个部分的节律(例如，阿尔法和德尔塔)。层流活动 在项目2和项目4中，同时从多个皮质和丘脑区域采集的轮廓将使我们能够 在网络级别上建模和约束节奏动态，这是项目1中分析的先验级别 3.在“迭代循环”中，模型将在细胞、细胞-电路和小范围内生成可测试的预测 在猴子身上测试的网络级别，以及在人类身上测试的更大的网络级别(核心A)，在每个 案例反馈到建模中。我们的具体目标是： 目的1：在主动感觉中建立丘脑皮质相互作用的模型。 目的2：模拟选择性丘脑皮质夹带对节律性输入的生理学作用。正在进行的R21 目标3：对编排有源传感不同工作模式的大规模电路进行建模。 中心协同效应：该项目将使用项目4中的丘脑和大脑皮层数据来模拟大脑皮层和 丘脑在选择性夹带到“外在”节律中的相互作用，以及来自项目2的数据以模拟大脑皮层 以及丘脑之间的相互作用，这是感觉输入的“内在”节奏采样的基础。经过计算后 模型包含了充分的经验性信息，结果使新的预测变得可检验。 生理学研究将被用来完善他们的分析。他们还将提供工具来解释 项目1和项目3分析中丘脑投射对皮质连贯性的影响。 模型预测将通过猴子的药理操作和直接大脑进行检验。 在猴子和选定的ECoG研究(核心A)中的刺激，结果将完善该模型。

Abstract We will use detailed biophysical (Dynamical Systems) modeling to pursue two large questions critical to integrating and understanding the results of Projects 1-4. What are the physiological origins of the brain rhythms studied empirically in Projects 1-4? How do network level rhythms depend on the physiological properties of the underlying neuronal ensembles? Modeling uses differential equation descriptions of physiology at the level of single cells, synapses and networks. Data from Projects 2 and 4, along with prior models and in-vitro findings, will help to build and refine physiologically-plausible cell circuit models that generate oscillations. Models will help investigate how local brain rhythms, periodic (and aperiodic) sensory inputs and top-down signals combine in Active Sensing. We will rigorously test questions concerning the neuron populations, interconnections and cellular processes (e.g., conductances) that generate specific rhythms (e.g., alpha and delta) in multiple parts of the brain during Active Sensing tasks. Laminar activity profiles sampled concurrently from multiple cortical and thalamic areas in Projects 2 and 4 will allow us to model and constrain rhythmic dynamics at a network level, which is the a-priori level of analysis in Projects 1 and 3. In an “iterative loop,” models will generate testable predictions at cellular, cell-circuit and and small network levels to be tested in monkeys, and at larger network levels to be tested in humans (Core A), in each case feeding back into the modeling. Our SPECIFIC AIMS are: AIM 1: Model thalamocortical interactions underlying intrinsic sampling rhythms in Active Sensing. AIM 2: Model the physiology of selective thalamocortical entrainment to rhythmic input. An ongoing R21 AIM 3: Model the large scale circuitry orchestrating distinct operational modes of Active Sensing.. CENTER SYNERGIES: This project will use thalamic and cortical data from Project 4 to model cortical and thalamic interactions in selective entrainment to “extrinsic” rhythms, and data from Project 2 to model cortical and thalamic interactions underlying “intrinsic” rhythmic sampling of sensory input. After the computational models have incorporated sufficient empirically-derived information, results that make testable new predictions for the physiology studies will be used to refine their analyses. They will also provide tools with which to explain the effects of thalamic projections on cortical coherences seen in the analyses of projects 1 and 3. Specific model predictions will be tested with phamacological manipulations in monkeys, and with direct brain stimulation in monkeys and in selected ECoG sstudies (Core A), and the results will refine the model.