• GABA
• chloride
• long-term potentiation
• sleep
• sleep deprivation
• synaptic inhibition
• synaptic plasticity

• Animals
• Sleep/physiology
• Mice
• Wakefulness/physiology
• Chlorides/metabolism
• Pyramidal Cells/physiology
• Synapses/physiology
• Neuronal Plasticity/physiology
• Long-Term Potentiation/physiology
• Cerebral Cortex/physiology
• Male
• Mice, Inbred C57BL
• Glutamic Acid/metabolism
• Membrane Potentials

• alpha rhythm
• aperiodic activity
• electroencephalography
• sleep deprivation
• sleepiness

• Humans
• Sleep Deprivation/physiopathology
• Male
• Female
• Adult
• Alpha Rhythm/physiology
• Electroencephalography
• Young Adult
• Occipital Lobe/physiopathology
• Occipital Lobe/physiology

• 32471095 MOST | National Natural Science Foundation of China (NSFC)
• 2021YFC2501500 MOST | National Key Research and Development Program of China (NKPs)

• internship and residency
• learning
• sleep
• systematic review

• calcium
• cognitive ageing
• healthy ageing
• hippocampus
• long-term potentiation
• longevity
• neuroinflammation
• synaptic plasticity

• Synaptic Tagging
• hippocampus
• long-term depression
• long-term potentiation
• memory
• synaptic plasticity
• synaptic tagging and capture

• Synapses/physiology
• Humans
• Neuronal Plasticity/physiology
• Brain/physiology
• Memory/physiology
• Animals
• Models, Neurological

• Ministry of Health
• NUS Research Scholarship
• Ministry of Education
• National University Health System

• hippocampus
• mechanism
• memory impairment
• progress
• sleep deprivation

• 81973744 the National Natural Science Foundation of China
• 81473579 the National Natural Science Foundation of China
• 2022-I2M-1-018 CAMS Innovation Fund for Medical Science
• 2022-I2M-2-001 CAMS Innovation Fund for Medical Science
• 7173267 the Beijing Natural Science Foundation

• DRD2 expression
• Growth hormone
• Spatial cognition
• TNF-α
• Total sleep deprivation
• miR-9 expression

• IEGs
• Zif268
• cell clusters
• fear memory
• functional organization
• hippocampus
• sleep

• Brain-derived neurotrophic factor
• Flavonoids
• Inflammation
• Memory
• Sleep deprivation

• PDE4B
• Roflumilast
• cAMP
• memory
• sleep deprivation
• synaptic proteins

• Alzheimer’s disease
• Epilepsy
• NREM sleep
• Sleep disorders
• Slow-wave sleep
• Subclinical epileptiform activity

• cell proliferation
• dentate gyrus
• fate determination
• hippocampus
• memory consolidation
• neuronal lineage

Insufficient sleep has been correlated to many physiological and psychoneurological disorders. Over the years, our understanding of the state of sleep has transcended from an inactive period of rest to a more active state involving important cellular and molecular processes. In addition, during sleep, electrophysiological changes also occur in pathways in specific regions of the mammalian central nervous system (CNS). Activity mediated synaptic plasticity in the CNS can lead to long-term and sometimes permanent strengthening and/or weakening synaptic strength affecting neuronal network behaviour. Memory consolidation and learning that take place during sleep cycles, can be affected by changes in synaptic plasticity during sleep disturbances. G-protein coupled receptors (GPCRs), with their versatile structural and functional attributes, can regulate synaptic plasticity in CNS and hence, may be potentially affected in sleep deprived conditions. In this review, we aim to discuss important functional changes that can take place in the CNS during sleep and sleep deprivation and how changes in GPCRs can lead to potential problems with therapeutics with pharmacological interventions.

• G-protein coupled receptors
• Metabotropic glutamate receptors
• Gamma-amino butyric acid-B receptor
• Synaptic plasticity
• Sleep deprivation
• Memory consolidation

• sleep deprivation
• cognitive dysfunction
• microglia
• cx3cr1 deficiency

• Animals
• Cognitive Dysfunction
• Mice
• Mice, Inbred C57BL
• Microglia
• Neuroinflammatory Diseases
• Sleep Deprivation

• Ashwagandha
• Ethnobotany
• Pharmacology
• Phytochemistry
• Toxicology
• Withania somnifera
• Withanolides

• Animals
• Antiviral Agents/isolation & purification
• Antiviral Agents/pharmacology
• COVID-19/virology
• Ethnopharmacology
• Humans
• Neuroprotective Agents/isolation & purification
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/toxicity
• Patient Safety
• Phytochemicals/isolation & purification
• Phytochemicals/pharmacology
• Phytochemicals/toxicity
• Plant Extracts/isolation & purification
• Plant Extracts/pharmacology
• Plant Extracts/toxicity
• Plant Roots
• Psychotropic Drugs/isolation & purification
• Psychotropic Drugs/pharmacology
• Psychotropic Drugs/toxicity
• Risk Assessment
• SARS-CoV-2/drug effects
• SARS-CoV-2/pathogenicity
• Withania/chemistry
• COVID-19 Drug Treatment

• Gene expression
• Hippocampus
• Memory
• RNA sequencing
• Sleep deprivation
• Transcription
• Transcriptome
• Translatome

• Animals
• Base Sequence
• Cell Nucleus/metabolism
• Cytoskeletal Proteins/genetics
• Dendrites/metabolism
• Gene Expression Regulation
• Gene Ontology
• Hippocampus/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Nerve Tissue Proteins/genetics
• Neurons/metabolism
• Protein Biosynthesis
• RNA Splicing
• RNA, Messenger/biosynthesis
• RNA, Messenger/genetics
• Sleep Deprivation/genetics
• Sleep Deprivation/rehabilitation
• Transcriptome

• P30 ES005605 NIEHS NIH HHS
• P50 HD103556 NICHD NIH HHS
• R01 AG062398 NIA NIH HHS
• T32 GM008629 NIGMS NIH HHS
• National Institute on Aging

• APP/PS1 transgenic mice
• Amyloid-β
• Chronic sleep deprivation
• Cognitive behavior
• Long-term potentiation
• Microglia

• Chronic insomnia disorder
• Functional connectivity
• Hippocampal subregions
• Short-term insomnia disorder

• Kynurenic-acid
• Kynurenine pathway
• brain
• sleep deprivation

Sleep is highly conserved across evolution, suggesting vital biological functions that are yet to be fully understood. Animals and humans experiencing partial sleep restriction usually exhibit detrimental physiological responses, while total and prolonged sleep loss could lead to death. The perturbation of sleep homeostasis is usually accompanied by an increase in hypothalamic–pituitary–adrenal (HPA) axis activity, leading to a rise in circulating levels of stress hormones (e.g. cortisol in humans, corticosterone in rodents). Such hormones follow a circadian release pattern under undisturbed conditions and participate in the regulation of sleep. The investigation of the consequences of sleep deprivation, from molecular changes to behavioural alterations, has been used to study the fundamental functions of sleep. However, the reciprocal relationship between sleep and the activity of the HPA axis is problematic when investigating sleep using traditional sleep-deprivation protocols that can induce stress per se. This is especially true in studies using rodents in which sleep deprivation is achieved by exogenous, and potentially stressful, sensory–motor stimulations that can undoubtedly confuse their conclusions. While more research is needed to explore the mechanisms underlying sleep loss and health, avoiding stress as a confounding factor in sleep-deprivation studies is therefore crucial. This review examines the evidence of the intricate links between sleep and stress in the context of experimental sleep deprivation, and proposes a more sophisticated research framework for sleep-deprivation procedures that could benefit from recent progress in biotechnological tools for precise neuromodulation, such as chemogenetics and optogenetics, as well as improved automated real-time sleep-scoring algorithms.

• glucocorticoids
• non-rapid eye movement sleep
• rapid eye movement sleep

Chronic sleep restriction in adolescents is widespread, yet we know little about how to apportion the limited amount of sleep obtained to minimize cognitive impairment: should sleep occur only nocturnally, or be split across separate nocturnal and daytime nap periods? This is particularly relevant to hippocampal-dependent cognitive functions that underpin several aspects of learning.

We assessed hippocampal function in four groups by evaluating short-term topographical memory with the Four Mountains Test (4MT). All participants began with 9 hours nocturnal time-in-bed (TIB) for 2 days before following different sleep schedules over the next 3 days. Each day, one group had 5 hours nocturnal TIB (5.0h; n = 30), another, 6.5 hours nocturnal TIB (6.5h; n = 29), and a third had 6.5 hours split into 5 hours nocturnal TIB and a 1.5 hour TIB daytime nap (5.0 + 1.5h; n = 29). A control group maintained 9 hours nocturnal TIB (9.0h; n = 30). The 4MT was administered mid-afternoon (1.5 hours after awakening for those who napped).

Performance of the 5.0h and 6.5h nocturnal TIB groups was significantly impaired relative to the 9.0h control group. Performance of participants on the split- sleep schedule (5.0 + 1.5h) did not significantly differ from controls.

These findings suggest that hippocampal function is sensitive to moderate multi-night sleep restriction, but deficits can be ameliorated by splitting sleep, at least for a period after waking from a daytime nap. While this split sleep schedule should not be considered a replacement for adequate nocturnal sleep, it appears to benefit the cognitive and neurophysiological functions that underpin learning in those who are chronically sleep deprived.

• memory
• nap
• sleep deprivation
• sleep restriction
• spatial memory
• split sleep
• topographical memory

• Animals
• Antidepressive Agents/pharmacology
• Antidepressive Agents/therapeutic use
• Depression/drug therapy
• Depression/pathology
• Depression/physiopathology
• Homeostasis/drug effects
• Humans
• Neuronal Plasticity/drug effects
• Randomized Controlled Trials as Topic
• Sleep/drug effects

• SAHA
• hippocampus
• late-LTP
• sleep deprivation
• synaptic capture
• synaptic tagging

• late-LTP
• metaplasticity
• p75NTR
• sleep deprivation
• synaptic capture
• synaptic tagging

• Actin Depolymerizing Factors/metabolism
• Animals
• Brain-Derived Neurotrophic Factor/metabolism
• Cyclic AMP/metabolism
• Cyclic AMP Response Element-Binding Protein/metabolism
• Cyclic AMP-Dependent Protein Kinases/metabolism
• Hippocampus/metabolism
• Lim Kinases/metabolism
• Male
• Memory
• Mice
• Mice, Inbred C57BL
• Neuronal Plasticity
• Phosphoric Diester Hydrolases/metabolism
• Receptors, Nerve Growth Factor/genetics
• Receptors, Nerve Growth Factor/metabolism
• Signal Transduction
• Sleep Deprivation/genetics
• Sleep Deprivation/metabolism
• Sleep Deprivation/physiopathology
• rho-Associated Kinases/metabolism
• rhoA GTP-Binding Protein/metabolism

• Consolidation
• Declarative memory
• Encoding
• Long-term memory
• Retrieval
• Sleep
• Sleep deprivation

• Brain/physiology
• Brain/physiopathology
• Humans
• Learning/physiology
• Memory/physiology
• Sleep/physiology
• Sleep Deprivation/psychology

• Dihydromyricetin
• Neuroprotection
• Oxidative stress
• Sleep deprivation
• Synaptic plasticity

• Acute Disease
• Animals
• Flavonols/pharmacology
• Flavonols/therapeutic use
• Maze Learning/drug effects
• Memory Disorders/complications
• Memory Disorders/drug therapy
• Memory Disorders/metabolism
• Memory Disorders/physiopathology
• Mice
• Neuronal Plasticity/drug effects
• Oxidative Stress/drug effects
• Sleep Deprivation/complications

• Glycogen
• Glymphatic system
• Hippocampal place cells
• Learning
• Memory
• Ocular dominance plasticity
• Synaptic homeostasis
• Synaptic plasticity

• Animals
• Brain/physiology
• Learning
• Memory
• Neuronal Plasticity/physiology
• Sleep/physiology

• R01 EY019022 NEI NIH HHS
• R01 HL114161 NHLBI NIH HHS

Posttraining consolidation, also known as offline learning, refers to neuroplastic processes and systemic reorganization by which newly acquired skills are converted from an initially transient state into a more permanent state. An extensive amount of research on cognitive and fine motor tasks has shown that sleep is able to enhance these processes, resulting in more stable declarative and procedural memory traces. On the other hand, limited evidence exists concerning the relationship between sleep and learning of gross motor skills. We are particularly interested in this relationship with the learning of gross motor skills in adulthood, such as in the case of sports, performing arts, devised experimental tasks, and rehabilitation practice. Thus, the present review focuses on sleep and gross motor learning (GML) in adults. The literature on the impact of sleep on GML, the consequences of sleep deprivation, and the influence of GML on sleep architecture were evaluated for this review. While sleep has proven to be beneficial for most gross motor tasks, sleep deprivation in turn has not always resulted in performance decay. Furthermore, correlations between motor performance and sleep parameters have been found. These results are of potential importance for integrating sleep in physiotherapeutic interventions, especially for patients with impaired gross motor functions.

• Hippocampus
• Metaplasticity
• Mouse
• Sleep deprivation
• Synaptic tagging and capture

• Animals
• Electric Stimulation
• Hippocampus/physiopathology
• Long-Term Potentiation
• Male
• Mice, Inbred C57BL
• Neurons/physiology
• Sleep Deprivation/physiopathology

• P01 AG017628 NIA NIH HHS
• P50 HL060287 NHLBI NIH HHS
• R01 MH117964 NIMH NIH HHS
• T32 HL007953 NHLBI NIH HHS

Mitochondrial dysfunction induced by mitochondria-related β-amyloid (Aβ) accumulation is increasingly being considered a novel risk factor for sporadic Alzheimer’s disease pathophysiology. The close relationship between chronic sleep restriction (CSR) and cortical Aβ elevation was confirmed recently. By assessing frontal cortical mitochondrial function (electron microscopy manifestation, cytochrome C oxidase concentration, ATP level, and mitochondrial membrane potential) and the levels of mitochondria-related Aβ in 9-month-old adult male C57BL/6J mice subjected to CSR and as an environmental control (CO) group, we aimed to evaluate the association of CSR with mitochondrial dysfunction and mitochondria-related Aβ accumulation. In this study, frontal cortical mitochondrial dysfunction was significantly more severe in CSR mice compared with CO animals. Furthermore, CSR mice showed higher mitochondria-associated Aβ, total Aβ, and mitochondria-related β-amyloid protein precursor (AβPP) levels compared with CO mice. In the CSR model, mouse frontal cortical mitochondrial dysfunction was correlated with mitochondria-associated Aβ and mitochondria-related AβPP levels. However, frontal cortical mitochondria-associated Aβ levels showed no significant association with cortical total Aβ and mitochondrial AβPP concentrations. These findings indicated that CSR-induced frontal cortical mitochondrial dysfunction and mitochondria-related Aβ accumulation, which was closely related to mitochondrial dysfunction under CSR.

• Anxiety
• Cognition
• Morin hydrate
• Oxidative stress
• Sleep deprivation

• Animals
• Anti-Anxiety Agents/pharmacology
• Antioxidants/pharmacology
• Behavior, Animal/drug effects
• Flavonoids/chemistry
• Flavonoids/pharmacology
• Hippocampus/drug effects
• Hippocampus/metabolism
• Male
• Maze Learning/drug effects
• Mice
• Neurons/drug effects
• Neuroprotective Agents/pharmacology
• Oxidative Stress/drug effects
• Sleep Deprivation/drug therapy

• declarative memory
• episodic memory
• learning

Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice. S-DEP increased the levels of TNFα but decreased PGRN levels in the hippocampus. The intracerebroventricular (ICV) injection of PGRN or intraperitoneal injection of TNFα synthesis blocker thalidomide (25 mg/kg), prevented the memory impairment and anxiety behaviors induced by S-DEP. PGRN treatment also restored dendritic spine density in the hippocampus CA1 region and neurogenesis in hippocampus dentate gyrus (DG). These results indicate that an imbalance between TNFα and PGRN contributes to memory impairment and thigmotaxis/anxiety caused by sleep deprivation.

• Aplysia
• learning and memory
• sleep deprivation

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.

Sleep deprivation is believed to lead to homeostatic increases in synaptic strength and reduced inducibility of associative LTP, based mainly on findings from animal studies. Here, Kuhn et al. demonstrate similar sleep-dependent synaptic plasticity changes in humans along with altered plasma BDNF levels.

• Brain-derived neurotrophic factor
• Histone acetylation
• Histone deacetylase
• Sleep deprivation
• Spatial memory

• Acetylation
• Animals
• Brain-Derived Neurotrophic Factor/genetics
• Brain-Derived Neurotrophic Factor/metabolism
• Epigenesis, Genetic/physiology
• Hippocampus/metabolism
• Histone Deacetylase 2/metabolism
• Histones/metabolism
• Male
• Memory Disorders/etiology
• Memory Disorders/metabolism
• Protein Processing, Post-Translational/genetics
• Rats, Wistar
• Sleep Deprivation/complications
• Sleep Deprivation/metabolism
• Spatial Memory/physiology

• Ashwagandha
• Cell survival
• Neuroprotection
• Sleep deprivation
• Synaptic plasticity

Sleep deprivation during pregnancy is a serious public health problem as it can affect the health of pregnant women and newborns. However, it is not well studied whether sleep deprivation at different stages of pregnancy has similar effects on emotional and cognitive functions of the offspring, and if so, the potential cellular mechanisms also remain poorly understood.

In the present study, the pregnant rats were subjected to sleep deprivation for 6 h per day by gentle handling during the first (gestational days 1–7), second (gestational days 8–14) and third trimester (gestational days 15–21) of pregnancy, respectively. The emotional and cognitive functions as well as hippocampal long-term potentiation (LTP) were tested in the offspring rats (postnatal days 42-56).

The offspring displayed impaired hippocampal-dependent spatial learning and memory, and increased depressive- and anxiety-like behaviors. Quantification of BrdU-positive cells revealed that adult hippocampal neurogenesis was significantly reduced compared to control. Electrophysiological recording showed that maternal sleep deprivation impaired hippocampal CA1 LTP and reduced basal synaptic transmission, as reflected by a decrease in the frequency and amplitude of miniature excitatory postsynaptic current in the hippocampal CA1 pyramidal neurons.

Taken together, these results suggest that maternal sleep deprivation at different stages of pregnancy disrupts the emotional and cognitive functions of the offspring that might be attributable to the suppression of hippocampal LTP and basal synaptic transmission.