Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex

Abstract

Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep–wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans.

Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need

“…Upon prolonged TDW, however, potentiation processes are expected to saturate, just as process-S dynamics themselves saturate. SD indeed is found to impair LTP capacity (47,48) that only sleep can restore. Our molecular data support a role of TDW in synaptic plasticity, as Hcrt ko/ko mouse lower TDW expression correlates with lower cortical expression of the plasticity-related transcripts Egr1/ Zif268, Per2, and Bdnf.…”

Sleep, synaptic homeostasis and neuronal firing rates

“…In the past 2–3 years several other studies were either explicitly designed to test SHY’s main idea [8–14], or interpreted their findings in light of SHY [15–17]. I will review these studies starting from those that used more direct measures of synaptic strength, such as number and size of synapses.…”

All You Need Is Sleep

“…Study by Kuhn et al (2016) also adds to a growing body of evidence from animal and human studies that support a close relationship between structural brain plasticity, and hence its functioning, and the sleep-wake cycle (Tononi and Cirelli, 2014). In addition to possible alterations in synaptic volume and number, significant changes in the interstitial brain space during sleep have also been shown (Xie et al, 2013).…”

“…Moreover, many sleep disorders are associated with major neuropsychiatric and neurodegenerative disorders (Emamian et al, 2016, Rosenzweig et al, 2015), and the duality of this link is further evident from interrelated improvements, or refractoriness of both, during the treatment. In a landmark study by Kuhn et al (2016) an increase in homeostatic plasticity (overall synaptic strength) and a partial occlusion of associative plasticity (transmission across single synapses) after sleep deprivation compared with sleep is demonstrated (Kuhn et al, 2016). This study adds another small but important step towards evidence for the synaptic homeostasis hypothesis of sleep–wake regulation (Tononi and Cirelli, 2014).…”

“…This study adds another small but important step towards evidence for the synaptic homeostasis hypothesis of sleep–wake regulation (Tononi and Cirelli, 2014). Combined, its results indicate that sleep may act to recalibrate synaptic plasticity in the human cortex and hence, to enable further plasticity during ensuing wakefulness (Kuhn et al, 2016). Dormio ergo sum ( Latin ), or perhaps, I exist/think/feel because I sleep.…”