CRCNS: Integrated Empirical and Multi-scale Modeling of Human Sleep Spindles

描述（由申请人提供）：神经振荡组织皮质-丘脑活动，它们在记忆、注意力和睡眠中的作用是系统神经科学的中心焦点。睡眠纺锤波是最突出的振荡之一，已经在许多层面上进行了研究，从生物物理层面来看，低阈值钙电流与起源于丘脑和皮层回路的11-15赫兹的峰状脉冲的起伏有关；在系统层面上，脑电图（EEG）和脑磁图（MEG）在颅骨外测量，在整个皮层的爆发模式中记录了大规模的空间和时间一致性（Destexhe和Sejnowski， 2001）。尽管有大量的生理、解剖和计算方面的研究，但仍有一些主要问题有待解决：在纺锤波期间，大脑皮层附近的部分是如何同步的？纺锤波是如何在大脑皮层中传播的？为什么在脑电图和脑磁图测量中同时观察到的纺锤波的时间模式存在差异？丘脑皮质系统的纺锤体活动对睡眠期间皮层重组和记忆巩固的影响是什么？我们建议通过一系列实验和建模技术来解决这些问题：1)将生物物理层面的详细模型与人类在深度电极电流源密度分析（CSD）记录层面的记录联系起来；2)将皮质回路的大规模简化模型与人类脑电图和脑磁图测量相关联。这是第一次将所有这些强大的经验和建模方法整合到一个单一的、多尺度的方法中，以理解基于位于皮层和丘脑不同层的神经元中发生的特定生物物理机制的头皮外宏观场测量的起源。

DESCRIPTION (provided by applicant): Neural oscillations organize cortico-thalamic activity, and their role in memory, attention and sleep are a central focus of systems neuroscience. Sleep spindles are among the most prominent oscillations, and have been studied at many levels of investigation, from the biophysical level, where the low threshold calcium currents are implicated in the waxing-and-waning 11-15 Hz bursts of spikes that originate in the thalamus and recruit cortical circuits, to the systems level where the electroencephalogram (EEG) and magnetoencephalogram (MEG) measured outside the skull register largescale spatial and temporal coherence in the bursting pattern across the cortex (Destexhe and Sejnowski, 2001). Despite the wealth of physiological, anatomical and computational studies, major questions remain to be resolved: How do nearby parts of the cortex become synchronized during spindles? How are spindles propagated across the cortex? Why is there a discrepancy between the temporal patterns of spindles simultaneously observed in EEG and MEG measurements? What are the consequences of spindle activity in thalamocortical systems for cortical reorganization and memory consolidation during sleep? We propose to attack these questions with a range of experimental and modeling techniques that 1) link detailed models at the biophysical level to recordings from humans at the level of current source density analysis (CSD) recordings from depth electrodes; and 2) relate large scale reduced models of cortical circuits to EEG and MEG measurements in humans. This is the first time that all of these powerful empirical and modeling approaches have been integrated into a single, multiscale approach to understanding the origin of macroscopic field measurements outside the scalp based on the specific biophysical mechanisms occurring in neurons located in different layers of the cortex and thalamus.