Dataset Information

Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle.

ABSTRACT: Sleep and brain glutamatergic signaling are homeostatically regulated. Recovery sleep following prolonged wakefulness restores efficient functioning of the brain, possibly by keeping glutamatergic signaling in a homeostatic range. Evidence in humans and mice suggested that metabotropic glutamate receptors of subtype-5 (mGluR5) contribute to the brain's coping mechanisms with sleep deprivation. Here, proton magnetic resonance spectroscopy in 31 healthy men was used to quantify the levels of glutamate (Glu), glutamate-to-glutamine ratio (GLX), and ?-amino-butyric-acid (GABA) in basal ganglia (BG) and dorsolateral prefrontal cortex on 3 consecutive days, after ~8 (baseline), ~32 (sleep deprivation), and ~8 hours (recovery sleep) of wakefulness. Simultaneously, mGluR5 availability was quantified with the novel radioligand for positron emission tomography, [18F]PSS232, and the blood levels of the mGluR5-regulated proteins, fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) were determined. The data revealed that GLX (p = 0.03) in BG (for Glu: p < 0.06) and the serum concentration of FMRP (p < 0.04) were increased after sleep loss. Other brain metabolites (GABA, N-acetyl-aspartate, choline, glutathione) and serum BDNF levels were not altered by sleep deprivation (pall > 0.6). By contrast, the night without sleep enhanced whole-brain, BG, and parietal cortex mGluR5 availability, which was normalized by recovery sleep (pall < 0.05). The findings provide convergent multimodal evidence that glutamatergic signaling is affected by sleep deprivation and recovery sleep. They support a role for mGluR5 and FMRP in sleep-wake regulation and warrant further studies to investigate their causality and relevance for regulating human sleep in health and disease. Clinical Trial Registration: www.clinicaltrials.gov (study identifier: NCT03813082).

SUBMITTER: Weigend S

PROVIDER: S-EPMC6802568 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle.

Weigend Susanne S Holst Sebastian C SC Treyer Valérie V O'Gorman Tuura Ruth L RL Meier Josefine J Ametamey Simon M SM Buck Alfred A Landolt Hans-Peter HP

Sleep 20191001 11

Sleep and brain glutamatergic signaling are homeostatically regulated. Recovery sleep following prolonged wakefulness restores efficient functioning of the brain, possibly by keeping glutamatergic signaling in a homeostatic range. Evidence in humans and mice suggested that metabotropic glutamate receptors of subtype-5 (mGluR5) contribute to the brain's coping mechanisms with sleep deprivation. Here, proton magnetic resonance spectroscopy in 31 healthy men was used to quantify the levels of gluta ...[more]

PMID: 31304973

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Project description:Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

Project description:ObjectivesConventional scoring of sleep provides little information about the process of transitioning between vigilance states. We applied the state space technique (SST) using frequency band ratios to follow normal maturation of different sleep/wake states, velocities of movements, and transitions between states of juvenile (postnatal day 34, P34) and young adult rats (P71).Design24-h sleep recordings of eight P34 and nine P71 were analyzed using conventional scoring criteria and SST one week following implantation of telemetric transmitter. SST is a non-categorical approach that allows novel quantitative and unbiased examination of vigilance-states dynamics and state transitions. In this approach, behavioral changes are described in a 2-dimensional state space that is derived from spectral characteristics of the electroencephalography.Measurements and resultsWith maturation sleep intensity declines, the duration of deep slow wave sleep (DSWS) and light slow wave sleep (LSWS) decreases and increases, respectively. Vigilance state determination, as a function of frequency, is not constant; there is a substantial shift to higher ratio 1 in all vigilance states except DSWS. Deep slow wave sleep decreases in adult relative to juvenile animals at all frequencies. P71 animals have 400% more trajectories from Wake to LSWS (p = 0.005) and vice versa (p = 0.005), and 100% more micro-arousals (p = 0.021), while trajectories from LSWS to DSWS (p = 0.047) and vice versa (p = 0.033) were reduced by 60%. In both juvenile and adult animals, no significant changes were found in sleep velocity at all regions of the 2-dimensional state space plot; suggesting that maturation has a partial effect on sleep stability.ConclusionsHere, we present novel and original evidence that SST enables visualization of vigilance-state intensity, transitions, and velocities that were not evident by traditional scoring methods. These observations provide new perspectives in sleep state dynamics and highlight the usefulness of this technique in exploring the development of sleep-wake activity.

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Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle.

Publications

Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep-wake cycle.

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