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

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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.