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.

Public Health Relevance

The goal of these studies is to help provide a scientific basis for treatment of sleep disorders as well as promote understanding of the relationship between microscopic neuronal circuit activity and macroscopic non-invasive EEG and MEG measures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
4R01EB009282-08
Application #
9107852
Study Section
Biomedical Imaging Technology B Study Section (BMIT-B)
Program Officer
Peng, Grace
Project Start
2008-09-08
Project End
2017-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
8
Fiscal Year
2016
Total Cost
$514,557
Indirect Cost
$90,748
Name
University of California San Diego
Department
Type
Other Domestic Higher Education
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Lewis, Laura D; Piantoni, Giovanni; Peterfreund, Robert A et al. (2018) A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans. Elife 7:
Rosen, B Q; Krishnan, G P; Sanda, P et al. (2018) Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics. J Neurosci Methods :
Muller, Lyle; Chavane, Frédéric; Reynolds, John et al. (2018) Cortical travelling waves: mechanisms and computational principles. Nat Rev Neurosci 19:255-268
Wei, Yina; Krishnan, Giri P; Komarov, Maxim et al. (2018) Differential roles of sleep spindles and sleep slow oscillations in memory consolidation. PLoS Comput Biol 14:e1006322
González, Oscar C; Shiri, Zahra; Krishnan, Giri P et al. (2018) Role of KCC2-dependent potassium efflux in 4-Aminopyridine-induced Epileptiform synchronization. Neurobiol Dis 109:137-147
Halgren, Milan; Fabó, Daniel; Ulbert, István et al. (2018) Superficial Slow Rhythms Integrate Cortical Processing in Humans. Sci Rep 8:2055
Hagler Jr, Donald J; Ulbert, István; Wittner, Lucia et al. (2018) Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers. J Neurosci 38:3013-3025
Gonzalez, Christopher E; Mak-McCully, Rachel A; Rosen, Burke Q et al. (2018) Theta Bursts Precede, and Spindles Follow, Cortical and Thalamic Downstates in Human NREM Sleep. J Neurosci 38:9989-10001
Krishnan, Giri P; Rosen, Burke Q; Chen, Jen-Yung et al. (2018) Thalamocortical and intracortical laminar connectivity determines sleep spindle properties. PLoS Comput Biol 14:e1006171
Tele?czuk, Bartosz; Dehghani, Nima; Le Van Quyen, Michel et al. (2017) Local field potentials primarily reflect inhibitory neuron activity in human and monkey cortex. Sci Rep 7:40211

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