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

描述(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。睡眠纺锤体是最显著的振荡之一，已在多个研究水平对其进行了研究，从生物物理水平(在生物物理水平上，低阈值钙电流参与了起源于丘脑并招募皮质回路的11-15赫兹峰脉冲的爆发)，到系统水平，在系统水平上测量到在颅骨外测量的脑电(EEG)和磁脑图(MEG)，显示了整个大脑皮质爆发模式的大尺度时空一致性(Destexhe和Sejnowski，2001)。尽管有丰富的生理学、解剖学和计算机研究，但主要问题仍然有待解决：大脑皮质的邻近部分如何在纺锤波期间同步？纺锤体是如何在皮质中传播的？为什么在脑电和脑磁图测量中同时观察到的纺锤波的时间模式之间存在差异？睡眠期间丘脑皮质系统中的纺锤体活动对皮质重组和记忆巩固有什么影响？我们建议用一系列实验和建模技术来解决这些问题，这些技术1)将生物物理水平上的详细模型与来自深度电极的电流源密度分析(CSD)记录水平上的人类记录联系起来；2)将大规模的皮质回路简化模型与人类的脑电和脑磁图测量联系起来。这是首次将所有这些强大的经验和建模方法集成到一个单一的、多尺度的方法中，以了解基于位于大脑皮层和丘脑不同层的神经元中发生的特定生物物理机制来理解头皮外宏观场测量的来源。

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.