scholarly journals Alterations in sleep, sleep spindle, and EEG power in mGluR5 knockout mice

2020 ◽  
Vol 123 (1) ◽  
pp. 22-33 ◽  
Author(s):  
David D. Aguilar ◽  
Robert E. Strecker ◽  
Radhika Basheer ◽  
James M. McNally
Keyword(s):  
Eye Movement ◽  
Metabotropic Glutamate Receptor ◽  
Neural Oscillations ◽  
Alpha Power ◽  
Rapid Eye Movement ◽  
Sleep Spindle ◽  
Rapid Eye Movement Sleep ◽  
Metabotropic Glutamate ◽  
Gamma Power ◽  
Abnormal Sleep

The type 5 metabotropic glutamate receptor (mGluR5) represents a novel therapeutic target for schizophrenia and other disorders. Schizophrenia is associated with progressive abnormalities in cortical oscillatory processes including reduced spindles (8–15 Hz) during sleep and increased delta (0.5–4 Hz)- and gamma-band activity (30–80 Hz) during wakefulness. mGluR5 knockout (KO) mice demonstrate many schizophrenia-like behaviors, including abnormal sleep. To examine the effects of mGluR5 on the maintenance of the neocortical circuitry responsible for such neural oscillations, we analyzed sleep/wake electroencephalographic (EEG) activity of mGluR5 KO mice at baseline, after 6 h of sleep deprivation, and during a visual method of cortical entrainment (visual steady state response). We hypothesized mGluR5-KO mice would exhibit translationally relevant abnormalities in sleep and neural oscillations that mimic schizophrenia. Power spectral and spindle density analyses were performed across 24-h EEG recordings in mGluR5-KO mice and wild-type (WT) controls. Novel findings in mGluR5 KO mice include deficits in sleep spindle density, wake alpha power, and 40-Hz visual task-evoked gamma power and phase locking. Sigma power (10–15 Hz), an approximation of spindle activity, was also reduced during non-rapid eye movement sleep transitions. Our observations on abnormal sleep/wake are generally in agreement with previous reports, although we did not replicate changes in rapid eye movement sleep. The timing of these phenotypes may suggest an impaired circadian process in mGluR5 KO mice. In conclusion, EEG phenotypes in mGluR5 KO mice resemble deficits observed in patients with schizophrenia. These findings implicate mGluR5-mediated pathways in several translationally relevant phenotypes associated with schizophrenia, and suggest that agents targeting this receptor may have harmful consequences on sleep health and daily patterns of EEG power. NEW & NOTEWORTHY Metabotropic glutamate receptor type 5 (mGluR5) knockout (KO) mice show several translationally relevant abnormalities in neural oscillatory activity associated with schizophrenia. These include deficits in sleep spindle density, sigma and alpha power, and 40-Hz task-evoked gamma power. The timing of these phenotypes suggests an impaired circadian process in these mice. Previously reported rapid eye movement sleep deficits in this model were not observed. These findings suggest mGluR5-enhancing drugs may improve sleep stability and sleep spindle density, which could impact memory and cognition.

Neural oscillations during non-rapid eye movement sleep as biomarkers of circuit dysfunction in schizophrenia

2014 ◽  
Vol 39 (7) ◽  
pp. 1091-1106 ◽  
Author(s):  
Richard J. Gardner ◽  
Flavie Kersanté ◽  
Matthew W. Jones ◽  
Ullrich Bartsch
Keyword(s):  
Eye Movement ◽  
Neural Oscillations ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep

scholarly journals Sleep spindles are resilient to extensive white matter deterioration

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Erlan Sanchez ◽  
Caroline Arbour ◽  
Héjar El-Khatib ◽  
Karine Marcotte ◽  
Hélène Blais ◽  
...  
Keyword(s):  
White Matter ◽  
Eye Movement ◽  
Control Group ◽  
Sleep Spindles ◽  
Rapid Eye Movement ◽  
Sleep Spindle ◽  
Rapid Eye Movement Sleep ◽  
Brain Injured ◽  
Healthy Control ◽  
The Brain

Abstract Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury (n = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group (n = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.

scholarly journals Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

2021 ◽  
pp. 026988112110056
Author(s):  
Gordon B Feld ◽  
Til O Bergmann ◽  
Marjan Alizadeh-Asfestani ◽  
Viola Stuke ◽  
Jan-Philipp Wriede ◽  
...  
Keyword(s):  
Eye Movement ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Declarative Memory ◽  
Rapid Eye Movement ◽  
Metabotropic Glutamate Receptor 5 ◽  
Memory Processing ◽  
Metabotropic Glutamate ◽  
Healthy Humans ◽  
Nonrem Sleep

Background: Sleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of non-rapid eye movement (NonREM) sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors does not affect sleep-dependent consolidation of declarative memory. Aims: The aim of this study was to investigate the role of metabotropic glutamate receptor 5 (mGluR5) in memory processing during sleep. Methods: In two placebo-controlled within-subject crossover experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II participants learned new word-pairs in the morning after sleep. Results/outcomes: Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memory-relevant EEG oscillations. In NonREM sleep, fenobam suppressed 12–15 Hz spindles but augmented 2–4 Hz delta waves, whereas in rapid eye movement (REM) sleep it suppressed 4–8 Hz theta and 16–22 Hz beta waves. Notably, under fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Conclusions/interpretations: Our findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.

scholarly journals Manipulating neural activity and sleep-dependent memory consolidation

Neuroforum ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Ghorbani ◽  
Lisa Marshall
Keyword(s):  
Eye Movement ◽  
Neural Activity ◽  
Memory Consolidation ◽  
Nrem Sleep ◽  
Neural Oscillations ◽  
Rapid Eye Movement ◽  
Hippocampus Dependent Memory

AbstractSleep contributes actively to the consolidation of many forms of memory. This review describes the neural oscillations of non-rapid eye movement (NREM) sleep, the structures underlying these oscillations and their relation to hippocampus-dependent memory consolidation. A main focus lies on the relation between inter- and intraregional interactions and their electrophysiological representation. Methods for modulating neural oscillations with the intent of affecting memory consolidation are presented.

scholarly journals Connectivity differences between consciousness and unconsciousness in non-rapid eye movement sleep: a TMS–EEG study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Minji Lee ◽  
Benjamin Baird ◽  
Olivia Gosseries ◽  
Jaakko O. Nieminen ◽  
Melanie Boly ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep
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