Microconnectomics of neocortex: a multiscale computer model

新皮质微连接组学：多尺度计算机模型

• 批准号: 8743695
• 负责人: William W Lytton
• 金额: $ 60.3万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8743695
• 关键词: Address; Algorithms; Apical; Area; Autistic Disorder; Brain; Brain Stem; Brodmann' s area; Cell model; Cell physiology; Cells; Cerebrum; Code; Complex; Computer Simulation; Corpus striatum structure; Coupled; Data; Data Set; Dendrites; Dependence; Disease; Evaluation; Event; Frequencies; Functional Magnetic Resonance Imaging; Hybrids; Ion Channel; Lasers; Limb structure; Link; Location; Measurement; Measures; Mediating; Microscopic; Modeling; Motor Cortex; Movement; Neocortex; Neuroanatomy; Output; Parkinson Disease; Pattern; Phase; Physiological; Process; Property; Prosthesis; Pyramidal Cells; Recording of previous events; Scanning; Signal Transduction; Simulate; Spinal Cord; Stream; Structure; Structure-Activity Relationship; Synapses; System; Testing; Time; Translating; base; brain machine interface; cell type; density; imaging modality; millisecond; multi-scale modeling; neocortical; neuronal cell body; optogenetics; parallel processing; postsynaptic; public health relevance; reconstruction; relating to nervous system; research study; signal processing; simulation

DESCRIPTION (provided by applicant): We will develop a multi-scale model of primary motor cortex (area M1) based on a rich experimental dataset obtained in ongoing studies. The model will range from the level of ion channels in dendrites, up to the level of the inputs from and outputs to other areas of cortex, a range of microns to centimeters, with a temporal range of milliseconds to 10 sec. We will evaluate dynamical interactions across scale, made more complicated by a structure that features long apical dendrites of Layer 5 pyramidal cells that reach across layers of cortex and thereby across scales. This feature produces complex structure-function relations: apical dendrites directly process inputs from different cortical layes for export from the local microcircuit (direct input/output). They also act within the scale hierarchy, forming a component of the local network which provides a parallel processing of inputs to produce outputs via the entire Layer 5 pyramidal cell ensemble. Layer 5 pyramids form two distinct groups: corticostriatal cells that project to striatum and to other cortical area, and corticospinal cells that project downwards to brainstem and spinal cord. Our dual-output hypothesis conceptualizes these as partially separable subcircuits anchored by the two massive cell types. We suggest that the one-way projection (corticostriatal to corticospinal) between these subcircuits effects a major code transformation: dominant corticocortical temporal coding (corticostriatal subcircuit) to dominant rate coding (corticospinal subcircuit). Importantly for ths hypothesis, the corticospinal pyramidal cells show linear activation properties with little adaptation. Our Aims proceed from low to high through sets of tightly-linked experiment and simulation, with predictions leading to experiments leading to modified simulations: 1. Simulate integration of synaptic signals in dendrites, based on densities of Ih and IA measured with cell activation at different dendritic locations (subcellular scale: 1-10¿m); 2. Model cell firing based on current clamp experiments (cell scale: 30-800¿m); 3. Create circuit-level models based on projection strength measurements (microcircuit scale: 2-5mm); 4. Use information theoretic and dynamical measures to evaluate SPI-STR code transformation hypothesis through input/output analysis (projection scale: 10-100mm). We predict that the neocortical circuit can either combine or multiplex signals, depending on tags based on location, frequency, phase, and amplitude of inputs.

描述（由适用提供）：我们将基于正在进行的研究中获得的丰富实验数据集开发一个多尺度的原发性运动皮层（区域M1）模型。该模型的范围从树突中的离子通道的水平，到输入和输出的水平到皮质的其他区域，一系列微米到厘米，暂时的毫秒至10秒。我们将评估跨音阶的动态相互作用，使一个结构更加复杂，该结构具有长的5层锥体细胞的顶端树突，这些树枝状细胞跨过皮质层，从而跨越鳞片。此功能会产生复杂的结构功能关系：顶端树突直接从不同皮层层进行输入以从局部微电路（直接输入/输出）导出。它们还在刻度层次结构内作用，形成了本地网络的一个组成部分，该组件提供了输入的并行处理，以通过整个第5层金字塔细胞组合产生输出。第5层金字塔构成了两个不同的组：将纹状体的皮质纹状体细胞和其他皮质区域投射到其他的皮质区域，以及向下投射到脑干和脊髓的皮质纹状体细胞。我们的双输出假设将这些假设概念化为两种大细胞类型锚定的部分分开的子电路。我们建议这些亚电路之间的单向项目（皮质纹状体至皮质纹状体）影响主要的代码转换：主要的皮质皮层临时编码（皮质机械性皮质亚电路）到显性速率编码（CortiCototrospilspinal subcircuit）。重要的是，对于Ths假设，皮质脊髓锥体细胞显示线性激活特性，几乎没有适应。我们的目标通过一组紧密链接的实验和模拟进行，并进行了预测，导致实验导致了修改的模拟：1。基于在不同的树突位置在不同的树突尺度上用细胞激活测得的IH和IA的合成信号的集成，在树突中的集成（1-10-0-0-10歌m）； 2。基于模型电池发射 在当前的夹具实验上（细胞尺度：30-800€）； 3。基于投影强度测量值（微电路量表：2-5mm）创建电路级模型； 4。使用信息理论和动态测量来通过输入/输出分析（投影量表：10-100mm）评估SPI-STR代码转换假设。我们预测，新皮层电路可以组合或多个信号，具体取决于基于输入的位置，频率，相位和放大器的标签。