The sleep relay—the role of the thalamus in central and decentral sleep regulation

Abstract

Surprisingly, the concept of sleep, its necessity and function, the mechanisms of action, and its elicitors are far from being completely understood. A key to sleep function is to determine how and when sleep is induced. The aim of this review is to merge the classical concepts of central sleep regulation by the brainstem and hypothalamus with the recent findings on decentral sleep regulation in local neuronal assemblies and sleep regulatory substances that create a scenario in which sleep is both local and use dependent. The interface between these concepts is provided by thalamic cellular and network mechanisms that support rhythmogenesis of sleep-related activity. The brainstem and the hypothalamus centrally set the pace for sleep-related activity throughout the brain. Decentral regulation of the sleep-wake cycle was shown in the cortex, and the homeostat of non-rapid-eye-movement sleep is made up by molecular networks of sleep regulatory substances, allowing individual neurons or small neuronal assemblies to enter sleep-like states. Thalamic neurons provide state-dependent gating of sensory information via their ability to produce different patterns of electrogenic activity during wakefulness and sleep. Many mechanisms of sleep homeostasis or sleep-like states of neuronal assemblies, e.g. by the action of adenosine, can also be found in thalamic neurons, and we summarize cellular and network mechanisms of the thalamus that may elicit non-REM sleep. It is argued that both central and decentral regulators ultimately target the thalamus to induce global sleep-related oscillatory activity. We propose that future studies should integrate ideas of central, decentral, and thalamic sleep generation.

Thalamic glutamate/glutamine in restless legs syndrome

“…11 This study focused on thalamic glutamatergic activity using as a surrogate measure total thalamic glutamate (Glu) and glutamine (Gln) concentration assessed by proton magnetic resonance spectroscopy (…”

“…The hyperpolarization of thalamocortical neurons provides a primary regulation for sleep spindle generation and for reduction of sensory inputs enabling cortical sleep. 11 Increased thalamocortical excitation would therefore be expected to produce both the increased wake time and decreased stage 2 sleep seen in patients with RLS. Moreover, REM sleep represents a more activated brain state that could be much less affected if at all by increased thalamic excitatory activity.…”

Sleep spindles are locally modulated by training on a brain–computer interface

“…These brief 12-to 15-Hz oscillations are generated by the reticular nucleus of the thalamus and grouped by the slow oscillation (<1 Hz) in the neocortex (3). The reticular nucleus is involved in gating sensory inputs and it is hypothesized that sleep spindles prevent incoming sensory information from reaching the neocortex during NREM sleep (4). This dissociation could provide a window for uninterrupted replay of recently instantiated memories and thus support sleep-dependent memory consolidation.…”

Homeostatic Sleep Pressure is the Primary Factor for Activation of Cortical nNOS/NK1 Neurons

“…Current hypotheses implicate sleep factors such as adenosine or cytokines that accumulate during waking, and increase the propensity and depth of sleep (Coulon et al, 2012;Krueger et al, 2008;Landolt, 2008;Porkka-Heiskanen and Kalinchuk, 2011;Szymusiak and McGinty, 2008). Sleep factors are thought to act by inhibiting wake-promoting neurons (Porkka-Heiskanen and Kalinchuk, 2011;Rainnie et al, 1994), but may also act directly on the cerebral cortex (Clinton et al, 2011;Szymusiak, 2010).…”