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: 8926428
• 负责人: William W Lytton
• 金额: $ 55.18万
• 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/8926428
• 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; Health; Hybrids; Ion Channel; Lasers; Limb Prosthesis; 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; Spinal Cord; Stream; Structure; Structure-Activity Relationship; Synapses; System; Testing; Time; Translating; base; brain machine interface; cell type; density; imaging modality; millisecond; model building; multi-scale modeling; neocortical; neuronal cell body; optogenetics; parallel processing; postsynaptic; 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（由申请人提供）：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初级运动皮层（M1区）的多尺度模型。该模型的范围将从树突中的离子通道的水平，到皮层其他区域的输入和输出的水平，范围为微米到厘米，时间范围为毫秒到10秒。我们将评估跨尺度的动态相互作用，由于具有第5层锥体细胞的长顶端树突的结构而变得更加复杂，这些树突跨越皮层层，从而跨越尺度。这个功能产生了复杂的结构-功能关系：顶端树突直接处理来自不同皮质层的输入，以便从局部微电路输出（直接输入/输出）。它们还在尺度层次结构中起作用，形成局部网络的一个组成部分，该局部网络提供输入的并行处理，以通过整个第5层金字塔细胞系综产生输出。 第5层锥体形成两个不同的组：投射到纹状体和其他皮质区域的皮质纹状体细胞，以及向下投射到脑干和脊髓的皮质脊髓细胞。我们的双输出假设将这些概念化为由两种大规模细胞类型锚定的部分可分离的子电路。我们认为，这些子电路之间的单向投影（皮质纹状体到皮质脊髓）影响一个主要的代码转换：显性皮质皮质时间编码（皮质纹状体子电路），以显性率编码（皮质脊髓子电路）。对这一假说重要的是，皮质脊髓锥体细胞表现出线性激活特性，几乎没有适应性。 我们的目标是通过一系列紧密联系的实验和模拟从低到高进行，预测导致实验导致修改的模拟：1。根据不同树突位置细胞激活测量的Ih和IA密度，模拟突触信号在树突中的整合（亚细胞尺度：1-10 μ m）; 2.基于模型细胞点火 电流钳实验（细胞规模：30-800 μ m）; 3.基于投影强度测量创建电路级模型（微电路规模：2- 5 mm）; 4.运用信息论和动力学方法，通过输入/输出分析（投影尺度：10- 100 mm）评估SPI-STR编码转换假设。我们预测，新皮层回路可以联合收割机或多路复用信号，这取决于基于位置，频率，相位和输入幅度的标签。