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Temporal interactions between non-rapid eye movement (NREM) sleep rhythms especially the coupling between cortical slow oscillations (SO, ∼1 Hz) and thalamic spindles (∼12 Hz) have been proposed to contribute to multi-regional interactions crucial for memory processing and cognitive ability. We investigated relationships between NREM sleep depth, sleep spindles and SO-spindle coupling regarding memory ability and memory consolidation in healthy humans. Findings underscore the functional relevance of spindle dynamics (slow versus fast), SO-phase, and most importantly NREM sleep depth for cognitive processing. Cross-frequency coupling analyses demonstrated stronger precise temporal coordination of slow spindles to SO down-state in N2 for subjects with higher general memory ability. A GLM model underscored this relationship, and furthermore that fast spindle properties were predictive of overnight memory consolidation. Our results suggest cognitive fingerprints dependent on conjoint fine-tuned SO-spindle temporal coupling, spindle properties, and brain sleep state.
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Reducing brain kynurenic acid synthesis precludes kynurenine‐induced sleep disturbances
Summary Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg−1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF‐04859989 (30 mg kg−1; s.c.); or (iv) PF‐04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non‐rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non‐rapid eye movement sleep delta power and sleep spindles. PF‐04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non‐rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics.
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- Award ID(s):
- 1852331
- PAR ID:
- 10524510
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Journal of Sleep Research
- Volume:
- 33
- Issue:
- 3
- ISSN:
- 0962-1105
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1111/jsr.14038
