Cellular and neurochemical basis of sleep stages in the thalamocortical network

Abstract

The link between the combined action of neuromodulators in the brain and global brain states remains a mystery. In this study, using biophysically realistic models of the thalamocortical network, we identified the critical intrinsic and synaptic mechanisms, associated with the putative action of acetylcholine (ACh), GABA and monoamines, which lead to transitions between primary brain vigilance states (waking, non-rapid eye movement sleep [NREM] and REM sleep) within an ultradian cycle. Using ECoG recordings from humans and LFP recordings from cats and mice, we found that during NREM sleep the power of spindle and delta oscillations is negatively correlated in humans and positively correlated in animal recordings. We explained this discrepancy by the differences in the relative level of ACh. Overall, our study revealed the critical intrinsic and synaptic mechanisms through which different neuromodulators acting in combination result in characteristic brain EEG rhythms and transitions between sleep stages.

DOI: http://dx.doi.org/10.7554/eLife.18607.001

eLife digest

There are several stages of sleep that cycle repeatedly through the night with each producing distinctive patterns of electrical activity in the brain. It is thought that these patterns may help us to remember things that have happened throughout the day. Cells in parts of the brain called the hypothalamus and the brainstem control transitions between sleep stages. They regulate the release of chemicals known as neuromodulators in many parts of the brain, including the cortex and thalamus, which play the roles in memory and learning. Researchers now know how the neuromodulators influence the properties of individual brain cells. However, it is not clear how coordinated action of many neuromodulators result in the patterns of electrical activity seen in the brain during each stage of sleep.

Krishnan et al. used a computer model to investigate how three of these neuromodulators – acetylcholine, histamine and GABA – shift electrical activity in the brain between sleep stages. The computer model was able to recreate the network of brain cells in the cortex and thalamus and how this network responds to the changes in the levels of neuromodulators. The study found that simultaneous and balanced changes of acetylcholine, histamine, and GABA work together to shift the brain between the stages of sleep and to initiate patterns of the brain electrical activity specific to the different sleep stages.

Krishnan et al. predict that the relative differences in the level of acetylcholine in the brains of humans, cats and mice may explain why different species have different patterns of electrical activity during sleep. The study also found that an anesthetic drug called propofol may induce sleep-like patterns of electrical activity in the human brain by affecting the levels of all three of the neuromodulators. More studies are needed to look at how the networks of cells in the cortex and thalamus communicate with the brainstem, and how changes in the levels of neuromodulators affect memory and learning.

DOI: http://dx.doi.org/10.7554/eLife.18607.002