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1
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Lucey BP. Sleep Alterations and Cognitive Decline. Semin Neurol 2025. [PMID: 40081821 DOI: 10.1055/a-2557-8422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Sleep disturbances and cognitive decline are intricately connected, and both are prevalent in aging populations and individuals with neurodegenerative disorders such as Alzheimer's disease (AD) and other dementias. Sleep is vital for cognitive functions including memory consolidation, executive function, and attention. Disruption in these processes is associated with cognitive decline, although causal evidence is mixed. This review delves into the bidirectional relationship between alterations in sleep and cognitive impairment, exploring key mechanisms such as amyloid-β accumulation, tau pathology, synaptic homeostasis, neurotransmitter dysregulation, oxidative stress, and vascular contributions. Evidence from both experimental research and population-based studies underscores the necessity of early interventions targeting sleep to mitigate risks of neurodegenerative diseases. A deeper understanding of the interplay between sleep and cognitive health may pave the way for innovative strategies to prevent or reduce cognitive decline through improved sleep management.
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Affiliation(s)
- Brendan P Lucey
- Department of Neurology, Washington University School of Medicine, St Louis, Missouri
- Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri
- Center On Biological Rhythms and Sleep, Washington University School of Medicine, St Louis, Missouri
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2
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Sheybani L, Frauscher B, Bernard C, Walker MC. Mechanistic insights into the interaction between epilepsy and sleep. Nat Rev Neurol 2025; 21:177-192. [PMID: 40065066 DOI: 10.1038/s41582-025-01064-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2025] [Indexed: 04/04/2025]
Abstract
Epidemiological evidence has demonstrated associations between sleep and epilepsy, but we lack a mechanistic understanding of these associations. If sleep affects the pathophysiology of epilepsy and the risk of seizures, as suggested by correlative evidence, then understanding these effects could provide crucial insight into the basic mechanisms that underlie the development of epilepsy and the generation of seizures. In this Review, we provide in-depth discussion of the associations between epilepsy and sleep at the cellular, network and system levels and consider the mechanistic underpinnings of these associations. We also discuss the clinical relevance of these associations, highlighting how they could contribute to improvements in the management of epilepsy. A better understanding of the mechanisms that govern the interactions between epilepsy and sleep could guide further research and the development of novel approaches to the management of epilepsy.
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Affiliation(s)
- Laurent Sheybani
- Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
- National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.
- NIHR University College London Hospitals Biomedical Research Centre, London, UK.
| | - Birgit Frauscher
- Department of Neurology, Duke University Medical Center, Durham, NC, USA
- Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
| | - Christophe Bernard
- Aix Marseille Université, INSERM, INS, Institute Neurosciences des Systèmes, Marseille, France
| | - Matthew C Walker
- Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK
- National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK
- NIHR University College London Hospitals Biomedical Research Centre, London, UK
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Ventura S, Mathieson SR, O'Toole JM, Livingstone V, Murray DM, Boylan GB. Infant sleep EEG features at 4 months as biomarkers of neurodevelopment at 18 months. Pediatr Res 2025:10.1038/s41390-025-03893-6. [PMID: 39979586 DOI: 10.1038/s41390-025-03893-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 01/10/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Sleep parameters evolve in parallel with neurodevelopment. Sleep participates in synaptic homeostasis and memory consolidation and infant sleep parameters correlate with later aspects of early childhood cognition. METHODS Typically developing, term-born infants had a diurnal sleep-EEG at 4 months and Griffiths III developmental assessment at 18 months. EEG analysis included sleep macrostructure (i.e. durations of total sleep and sleep stages, and latencies to sleep and REM), sleep spindle features, and quantitative EEG features (qEEG): interhemispheric connectivity and spectral power. We assessed the correlations between these EEG features and Griffiths III quotients. RESULTS Sleep recordings from 92 infants were analyzed. Sleep latency was positively associated with the Griffiths III Foundations of Learning subscale and N3 sleep duration was positively correlated with the Personal-Social-Emotional subscale. Sleep spindle synchrony was negatively associated with Eye and Hand Coordination, Personal-Social-Emotional, Gross Motor, and General Development quotients. Sleep spindle duration was negatively associated with the Personal-Social-Emotional and Gross Motor subscales. In some sleep states, delta 1 and 2 EEG spectral power and interhemispheric coherence measures were correlated with subscale quotients. CONCLUSION Certain sleep features in the EEG of 4-month-old infants are associated with neurodevelopment at 18 months and may be useful early biomarkers of neurodevelopment. IMPACT This study shows that the EEG during infant sleep may provide insights into later neurodevelopmental outcomes. We have examined novel EEG sleep spindle features and shown that spindle duration and synchrony may help predict neurodevelopmental outcomes. Sleep macrostructure elements such as latency to sleep, N3 duration, and qEEG features such as interhemispheric coherence and spectral power measures at 4 months may be useful for the assessment of future neurodevelopmental outcomes. Due to exceptional neuroplasticity in infancy, EEG biomarkers of neurodevelopment may support early and targeted intervention to optimize outcomes.
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Affiliation(s)
- Soraia Ventura
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics & Child Health, University College Cork, Cork, Ireland
| | - Sean R Mathieson
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics & Child Health, University College Cork, Cork, Ireland
| | - John M O'Toole
- INFANT Research Centre, University College Cork, Cork, Ireland
| | - Vicki Livingstone
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics & Child Health, University College Cork, Cork, Ireland
| | - Deirdre M Murray
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics & Child Health, University College Cork, Cork, Ireland
| | - Geraldine B Boylan
- INFANT Research Centre, University College Cork, Cork, Ireland.
- Department of Paediatrics & Child Health, University College Cork, Cork, Ireland.
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Fasiello E, Galbiati A, Ferini-Strambi L. Impact of sleep deprivation on dynamic functional connectivity states. HANDBOOK OF CLINICAL NEUROLOGY 2025; 206:27-36. [PMID: 39864929 DOI: 10.1016/b978-0-323-90918-1.00012-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
Sleep deprivation (SD) is an experimental procedure to study the effects of sleep loss on the human brain. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), have been pivotal in studying these effects. The present chapter aims to retrace the state of the art regarding the literature that examines the SD effects on the brain through functional connectivity (FC) evaluated in fMRI and EEG settings, separately. Specifically, we focused on the cognitive domains mainly affected by sleep loss and the underlying brain connectivity alterations. SD disrupts homeostatic and circadian processes, negatively affecting cognitive and cerebral functionality explored through FC. All evidence confirms the detrimental role of SD on brain connectivity impacting several resting-state networks and resulting in cognitive impairments. To conclude, SD may offer useful insights into pathogenic mechanisms likely resembling those induced by chronic sleep loss that might find their application in the clinical context.
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Affiliation(s)
- Elisabetta Fasiello
- Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Galbiati
- Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luigi Ferini-Strambi
- Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
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5
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Inami S, Koh K. Sleep induced by mechanosensory stimulation provides cognitive and health benefits in Drosophila. Sleep 2024; 47:zsae226. [PMID: 39331490 DOI: 10.1093/sleep/zsae226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/08/2024] [Indexed: 09/29/2024] Open
Abstract
STUDY OBJECTIVES Sleep is a complex phenomenon regulated by various factors, including sensory input. Anecdotal observations have suggested that gentle rocking helps babies fall asleep, and experimental studies have verified that rocking promotes sleep in both humans and mice. Recent studies have expanded this understanding, demonstrating that gentle vibration also induces sleep in Drosophila. Natural sleep serves multiple functions, including learning and memory, synaptic downscaling, and reduction of harmful substances associated with neurodegenerative diseases. Here, we investigated whether vibration-induced sleep (VIS) provides similar cognitive and health benefits in Drosophila. METHODS We administered gentle vibration to flies that slept very little due to a forced activation of wake-promoting neurons and investigated how the vibration influenced learning and memory in the courtship conditioning paradigm. Additionally, we examined the effects of VIS on synaptic downscaling by counting synaptic varicosities of select neurons. Finally, we determined whether vibration could induce sleep in Drosophila models of Alzheimer's disease (AD) and suppress the accumulation of Amyloid β (Aβ) and Tubulin Associated Unit (TAU). RESULTS VIS enhanced performance in a courtship conditioning paradigm and reduced the number of synaptic varicosities in select neurons. Moreover, vibration improved sleep in Drosophila models of AD, reducing Aβ and TAU levels. CONCLUSIONS Mechanosensory stimulation offers a promising noninvasive avenue for enhancing sleep, potentially providing associated cognitive and health benefits.
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Affiliation(s)
- Sho Inami
- Department of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, USA
| | - Kyunghee Koh
- Department of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, USA
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Yoon S, Lee S, Joo Y, Ha E, Hong H, Song Y, Lee H, Kim S, Suh C, Lee CJ, Lyoo IK. Variations in Brain Glutamate and Glutamine Levels Throughout the Sleep-Wake Cycle. Biol Psychiatry 2024:S0006-3223(24)01785-2. [PMID: 39643103 DOI: 10.1016/j.biopsych.2024.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 10/25/2024] [Accepted: 11/21/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Glutamatergic signaling is essential for modulating synaptic plasticity and cognition. However, the dynamics of glutamatergic activity over the 24-hour sleep-wake cycle, particularly in relation to sleep, remain poorly understood. In this study, we aimed to investigate diurnal variations in brain Glx levels-representing the combined concentrations of glutamate and glutamine-in humans and to explore their implications for cognitive performance and sleep pressure. METHODS We conducted 2 independent experiments to measure Glx levels across the sleep-wake cycle using proton magnetic resonance spectroscopy. In experiment 1, 14 participants underwent 13 hours of Glx measurements during a typical sleep-wake cycle. Experiment 2 extended these measurements to an around-the-clock observation over a 6-day period. This period included 2 days of normal sleep-wake cycles, 24 hours of enforced wakefulness, and a 3-day recovery phase. Seven participants took part in experiment 2. RESULTS The study observed that brain Glx levels increased during wakefulness and decreased during sleep. Notably, Glx levels were lower during enforced wakefulness than during normal wakefulness. Reduced Glx levels were associated with diminished cognitive performance, while greater Glx exposure over the preceding 24 hours correlated with increased sleep pressure. CONCLUSIONS These findings suggest that Glx accumulation may contribute to increased sleep pressure, while its reduction appears to support wakefulness. These observations, together with the diurnal variations in Glx levels, underscore the dynamic nature of glutamatergic activity across the daily cycle. Further research is warranted to explore the potential role of sleep in regulating glutamatergic homeostasis.
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Affiliation(s)
- Sujung Yoon
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, South Korea
| | - Suji Lee
- Division of Psychology and Cognitive Science, Seoul Women's University, Seoul, South Korea
| | - Yoonji Joo
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea
| | - Eunji Ha
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea
| | - Haejin Hong
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea
| | - Yumi Song
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, South Korea
| | - Hyangwon Lee
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, South Korea
| | - Shinhye Kim
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, South Korea
| | - Chaewon Suh
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea
| | - C Justin Lee
- Center for Cognition and Sociality, Institute for Basic Science, Daejeon, South Korea
| | - In Kyoon Lyoo
- Ewha Brain Institute, Ewha Womans University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, South Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
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Crowley R, Alderman E, Javadi AH, Tamminen J. A systematic and meta-analytic review of the impact of sleep restriction on memory formation. Neurosci Biobehav Rev 2024; 167:105929. [PMID: 39427809 DOI: 10.1016/j.neubiorev.2024.105929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/06/2024] [Accepted: 10/17/2024] [Indexed: 10/22/2024]
Abstract
Modern life causes a quarter of adults and half of teenagers to sleep for less than is recommended (Kocevska et al., 2021). Given well-documented benefits of sleep on memory, we must understand the cognitive costs of short sleep. We analysed 125 sleep restriction effect sizes from 39 reports involving 1234 participants. Restricting sleep (3-6.5 hours) compared to normal sleep (7-11 hours) negatively affects memory formation with a small effect size (Hedges' g = 0.29, 95 % CI = [0.13, 0.44]). We detected no evidence for publication bias. When sleep restriction effect sizes were compared with 185 sleep deprivation effect sizes (Newbury et al., 2021) no statistically significant difference was found, suggesting that missing some sleep has similar consequences for memory as not sleeping at all. When the analysis was restricted to post-encoding, rather than pre-encoding, sleep loss, sleep deprivation was associated with larger memory impairment than restriction. Our findings are best accounted for by the sequential hypothesis which emphasises complementary roles of slow-wave sleep and REM sleep for memory.
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Affiliation(s)
- Rebecca Crowley
- Department of Psychology, Royal Holloway, University of London, Egham TW20 0EX, United Kingdom.
| | - Eleanor Alderman
- Department of Psychology, Royal Holloway, University of London, Egham TW20 0EX, United Kingdom.
| | | | - Jakke Tamminen
- Department of Psychology, Royal Holloway, University of London, Egham TW20 0EX, United Kingdom.
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Massimini M, Corbetta M, Sanchez-Vives MV, Andrillon T, Deco G, Rosanova M, Sarasso S. Sleep-like cortical dynamics during wakefulness and their network effects following brain injury. Nat Commun 2024; 15:7207. [PMID: 39174560 PMCID: PMC11341729 DOI: 10.1038/s41467-024-51586-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 08/07/2024] [Indexed: 08/24/2024] Open
Abstract
By connecting old and recent notions, different spatial scales, and research domains, we introduce a novel framework on the consequences of brain injury focusing on a key role of slow waves. We argue that the long-standing finding of EEG slow waves after brain injury reflects the intrusion of sleep-like cortical dynamics during wakefulness; we illustrate how these dynamics are generated and how they can lead to functional network disruption and behavioral impairment. Finally, we outline a scenario whereby post-injury slow waves can be modulated to reawaken parts of the brain that have fallen asleep to optimize rehabilitation strategies and promote recovery.
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Grants
- The authors thank Dr Ezequiel Mikulan, Dr Silvia Casarotto, Dr Andrea Pigorini, Dr Simone Russo, and Dr Pilleriin Sikka for their help and comments on the manuscript draft and illustrations. This work was financially supported by the following entities: ERC-2022-SYG Grant number 101071900 Neurological Mechanisms of Injury and Sleep-like Cellular Dynamics (NEMESIS); Italian National Recovery and Resilience Plan (NRRP), M4C2, funded by the European Union - NextGenerationEU (Project IR0000011, CUP B51E22000150006, “EBRAINS-Italy”); European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No.945539 (Human Brain Project SGA3); Tiny Blue Dot Foundation; Canadian Institute for Advanced Research (CIFAR), Canada; Italian Ministry for Universities and Research (PRIN 2022); Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), Project ERAPERMED2019–101, GA 779282; CORTICOMOD PID2020-112947RB-I00 financed by MCIN/ AEI /10.13039/501100011033; Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO) Grant Agreement number 55403; Ministry of Health, Italy (RF-2008 -12366899) Brain connectivity measured with high-density electroencephalography: a novel neurodiagnostic tool for stroke- NEUROCONN; BIAL foundation grant (Grant Agreement number 361/18); H2020 European School of Network Neuroscience (euSNN); H2020 Visionary Nature Based Actions For Heath, Wellbeing & Resilience in Cities (VARCITIES); Ministry of Health Italy (RF-2019-12369300): Eye-movement dynamics during free viewing as biomarker for assessment of visuospatial functions and for closed-loop rehabilitation in stroke (EYEMOVINSTROKE).
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Affiliation(s)
- Marcello Massimini
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
| | - Maurizio Corbetta
- Department of Neuroscience and Padova Neuroscience Center (PNC), University of Padova, Padova, Italy
- Veneto Institute of Molecular Medicine (VIMM), Padova, Italy
| | - Maria V Sanchez-Vives
- Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - Thomas Andrillon
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Mov'it team, Inserm, CNRS, Paris, France
- Monash Centre for Consciousness and Contemplative Studies, Faculty of Arts, Monash University, Melbourne, VIC, Australia
| | - Gustavo Deco
- Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain
- Department of Information and Communication Technologies, Universitat Pompeu Fabra, Center for Brain and Cognition, Computational Neuroscience Group, Barcelona, Spain
| | - Mario Rosanova
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Simone Sarasso
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
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Leach S, Krugliakova E, Sousouri G, Snipes S, Skorucak J, Schühle S, Müller M, Ferster ML, Da Poian G, Karlen W, Huber R. Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults. Sci Rep 2024; 14:19184. [PMID: 39160150 PMCID: PMC11333484 DOI: 10.1038/s41598-024-67701-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 07/15/2024] [Indexed: 08/21/2024] Open
Abstract
Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.
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Affiliation(s)
- Sven Leach
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Elena Krugliakova
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
| | - Georgia Sousouri
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Mobile Health Systems Lab, Department of Health Sciences and Technology, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, Switzerland
- Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland
| | - Sophia Snipes
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jelena Skorucak
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Selina Schühle
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Manuel Müller
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Maria Laura Ferster
- Mobile Health Systems Lab, Department of Health Sciences and Technology, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, Switzerland
| | - Giulia Da Poian
- Sensory-Motor Systems Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Walter Karlen
- Mobile Health Systems Lab, Department of Health Sciences and Technology, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, Switzerland
- Institute of Biomedical Engineering, Faculty of Engineering, Computer Science and Psychology, Ulm University, Ulm, Germany
| | - Reto Huber
- Child Development Centre and Children's Research Centre, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
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Liu J, Niethard N, Lun Y, Dimitrov S, Ehrlich I, Born J, Hallschmid M. Slow-wave sleep drives sleep-dependent renormalization of synaptic AMPA receptor levels in the hypothalamus. PLoS Biol 2024; 22:e3002768. [PMID: 39163472 PMCID: PMC11364421 DOI: 10.1371/journal.pbio.3002768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 08/30/2024] [Accepted: 07/25/2024] [Indexed: 08/22/2024] Open
Abstract
According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.e., a pivotal center of homeostatic regulation of bodily functions including sleep itself. We show that sleep, in parallel with the synaptic down-regulation in neocortical networks, down-regulates the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hypothalamus of rats. Most robust decreases after sleep were observed at both sites for AMPARs containing the GluA1 subunit. Comparing the effects of selective rapid eye movement (REM) sleep and total sleep deprivation, we moreover provide experimental evidence that slow-wave sleep (SWS) is the driving force of the down-regulation of AMPARs in hypothalamus and neocortex, with no additional contributions of REM sleep or the circadian rhythm. SWS-dependent synaptic down-regulation was not linked to EEG slow-wave activity. However, spindle density during SWS predicted relatively increased GluA1 subunit levels in hypothalamic synapses, which is consistent with the role of spindles in the consolidation of memory. Our findings identify SWS as the main driver of the renormalization of synaptic strength during sleep and suggest that SWS-dependent synaptic renormalization is also implicated in homeostatic control processes in the hypothalamus.
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Affiliation(s)
- Jianfeng Liu
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
| | - Niels Niethard
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
| | - Yu Lun
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
| | - Stoyan Dimitrov
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
| | - Ingrid Ehrlich
- Department of Neurobiology, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, Stuttgart, Germany
| | - Jan Born
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
- Center for Integrative Neuroscience, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University Tübingen (IDM), Tübingen, Germany
- German Center for Mental Health (DZPG), Tübingen, Germany
| | - Manfred Hallschmid
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University Tübingen (IDM), Tübingen, Germany
- German Center for Mental Health (DZPG), Tübingen, Germany
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11
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Inami S, Koh K. Sleep induced by mechanosensory stimulation provides cognitive and health benefits in Drosophila. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.07.10.602891. [PMID: 39026689 PMCID: PMC11257551 DOI: 10.1101/2024.07.10.602891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Study Objectives Sleep is a complex phenomenon regulated by various factors, including sensory input. Anecdotal observations have suggested that gentle rocking helps babies fall asleep, and experimental studies have verified that rocking promotes sleep in both humans and mice. Recent studies have expanded this understanding, demonstrating that gentle vibration also induces sleep in Drosophila. Natural sleep serves multiple functions, including learning and memory, synaptic downscaling, and clearance of harmful substances associated with neurodegenerative diseases. Here, we investigated whether vibration-induced sleep provides similar cognitive and health benefits in Drosophila. Methods We administered gentle vibration to flies that slept very little due to a forced activation of wake-promoting neurons and investigated how the vibration influenced learning and memory in the courtship conditioning paradigm. Additionally, we examined the effects of VIS on synaptic downscaling by counting synapse numbers of select neurons. Finally, we determined whether vibration could induce sleep in Drosophila models of Alzheimer's disease (AD) and promote the clearance of Amyloid b (Ab) and Tubulin Associated Unit (TAU). Results Vibration-induced sleep enhanced performance in a courtship conditioning paradigm and reduced the number of synapses in select neurons. Moreover, vibration improved sleep in Drosophila models of AD, promoting the clearance of Ab and TAU. Conclusions Mechanosensory stimulation offers a promising non-invasive avenue for enhancing sleep, potentially providing associated cognitive and health benefits.
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Affiliation(s)
- Sho Inami
- Department of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University
| | - Kyunghee Koh
- Department of Neuroscience and the Farber Institute for Neurosciences, Thomas Jefferson University
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12
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Maboudi K, Giri B, Miyawaki H, Kemere C, Diba K. Retuning of hippocampal representations during sleep. Nature 2024; 629:630-638. [PMID: 38720085 PMCID: PMC11472358 DOI: 10.1038/s41586-024-07397-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 04/09/2024] [Indexed: 05/18/2024]
Abstract
Hippocampal representations that underlie spatial memory undergo continuous refinement following formation1. Here, to track the spatial tuning of neurons dynamically during offline states, we used a new Bayesian learning approach based on the spike-triggered average decoded position in ensemble recordings from freely moving rats. Measuring these tunings, we found spatial representations within hippocampal sharp-wave ripples that were stable for hours during sleep and were strongly aligned with place fields initially observed during maze exploration. These representations were explained by a combination of factors that included preconfigured structure before maze exposure and representations that emerged during θ-oscillations and awake sharp-wave ripples while on the maze, revealing the contribution of these events in forming ensembles. Strikingly, the ripple representations during sleep predicted the future place fields of neurons during re-exposure to the maze, even when those fields deviated from previous place preferences. By contrast, we observed tunings with poor alignment to maze place fields during sleep and rest before maze exposure and in the later stages of sleep. In sum, the new decoding approach allowed us to infer and characterize the stability and retuning of place fields during offline periods, revealing the rapid emergence of representations following new exploration and the role of sleep in the representational dynamics of the hippocampus.
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Affiliation(s)
- Kourosh Maboudi
- Dept of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA
- Dept of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
| | - Bapun Giri
- Dept of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA
- Dept of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
| | - Hiroyuki Miyawaki
- Dept of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
- Osaka Metropolitan University, Osaka, Japan
| | - Caleb Kemere
- Dept of Electrical and Computer Engineering, Rice University, Houston, TX, USA
| | - Kamran Diba
- Dept of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
- Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA.
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13
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Slutsky I. Linking activity dyshomeostasis and sleep disturbances in Alzheimer disease. Nat Rev Neurosci 2024; 25:272-284. [PMID: 38374463 DOI: 10.1038/s41583-024-00797-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2024] [Indexed: 02/21/2024]
Abstract
The presymptomatic phase of Alzheimer disease (AD) starts with the deposition of amyloid-β in the cortex and begins a decade or more before the emergence of cognitive decline. The trajectory towards dementia and neurodegeneration is shaped by the pathological load and the resilience of neural circuits to the effects of this pathology. In this Perspective, I focus on recent advances that have uncovered the vulnerability of neural circuits at early stages of AD to hyperexcitability, particularly when the brain is in a low-arousal states (such as sleep and anaesthesia). Notably, this hyperexcitability manifests before overt symptoms such as sleep and memory deficits. Using the principles of control theory, I analyse the bidirectional relationship between homeostasis of neuronal activity and sleep and propose that impaired activity homeostasis during sleep leads to hyperexcitability and subsequent sleep disturbances, whereas sleep disturbances mitigate hyperexcitability via negative feedback. Understanding the interplay among activity homeostasis, neuronal excitability and sleep is crucial for elucidating the mechanisms of vulnerability to and resilience against AD pathology and for identifying new therapeutic avenues.
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Affiliation(s)
- Inna Slutsky
- Department of Physiology and Pharmacology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
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14
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Snipes S, Krugliakova E, Jaramillo V, Volk C, Furrer M, Studler M, LeBourgeois M, Kurth S, Jenni OG, Huber R. Wake EEG oscillation dynamics reflect both sleep need and brain maturation across childhood and adolescence. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.24.581878. [PMID: 38463948 PMCID: PMC10925212 DOI: 10.1101/2024.02.24.581878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
An objective measure of brain maturation is highly insightful for monitoring both typical and atypical development. Slow wave activity, recorded in the sleep electroencephalogram (EEG), reliably indexes changes in brain plasticity with age, as well as deficits related to developmental disorders such as attention-deficit hyperactivity disorder (ADHD). Unfortunately, measuring sleep EEG is resource-intensive and burdensome for participants. We therefore aimed to determine whether wake EEG could likewise index developmental changes in brain plasticity. We analyzed high-density wake EEG collected from 163 participants 3-25 years old, before and after a night of sleep. We compared two measures of oscillatory EEG activity, amplitudes and density, as well as two measures of aperiodic activity, intercepts and slopes. Furthermore, we compared these measures in patients with ADHD (8-17 y.o., N=58) to neurotypical controls. We found that wake oscillation amplitudes behaved the same as sleep slow wave activity: amplitudes decreased with age, decreased after sleep, and this overnight decrease decreased with age. Oscillation densities were also substantially age-dependent, decreasing overnight in children and increasing overnight in adolescents and adults. While both aperiodic intercepts and slopes decreased linearly with age, intercepts decreased overnight, and slopes increased overnight. Overall, our results indicate that wake oscillation amplitudes track both development and sleep need, and overnight changes in oscillation density reflect some yet-unknown shift in neural activity around puberty. No wake measure showed significant effects of ADHD, thus indicating that wake EEG measures, while easier to record, are not as sensitive as those during sleep.
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Affiliation(s)
- Sophia Snipes
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Elena Krugliakova
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Donders Institute, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Valeria Jaramillo
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- School of Psychology, University of Surrey, Guildford, UK
- Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
- UK Dementia Research Institute Care Research and Technology Centre, Imperial College London and the University of Surrey, Guildford, UK
| | - Carina Volk
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Melanie Furrer
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Mirjam Studler
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Social Neuroscience and Social Psychology, Institute of Psychology, University of Bern, Bern, Switzerland
| | - Monique LeBourgeois
- University of Colorado at Boulder, Department of Integrative Physiology, Boulder, Colorado, USA
- The Warren Alpert Medical School of Brown University, Department of Psychiatry and Human Behavior, Providence, Rhode Island, USA
- In memoriam
| | - Salome Kurth
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Psychology, University of Fribourg, Fribourg, Switzerland
- Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland
| | - Oskar G Jenni
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Reto Huber
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Switzerland
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15
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Zhang Q, Hou YZ, Ding H, Shu YP, Li J, Chen XZ, Li JL, Lou Q, Wang DX. Alterations of sleep deprivation on brain function: A coordinate-based resting-state functional magnetic resonance imaging meta-analysis. World J Psychiatry 2024; 14:315-329. [PMID: 38464778 PMCID: PMC10921288 DOI: 10.5498/wjp.v14.i2.315] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/21/2023] [Accepted: 01/03/2024] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function. Although numerous neuroimaging studies have explored the neural correlates of sleep loss, inconsistencies persist in the reported results, necessitating an investigation into the consistent brain functional changes resulting from sleep loss. AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases. Two meta-analytic methods, signed differential mapping (SDM) and activation likelihood estimation (ALE), were employed to analyze functional magnetic resonance imaging (fMRI) data. METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29, 2023. Studies that met specific inclu-sion criteria, focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered. A total of 21 studies were selected for SDM and ALE meta-analyses. RESULTS Twenty-one studies, including 23 experiments and 498 subjects, were included. Compared to pre-sleep deprivation, post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule. SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus, left middle frontal gyrus, corpus callosum, and right cuneus. CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation, notably the left medial frontal gyrus and corpus callosum, shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.
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Affiliation(s)
- Qin Zhang
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
- Department of Radiology, Guizhou Provincial People’s Hospital, Guiyang 550000, Guizhou Province, China
| | - Yong-Zhe Hou
- Department of Psychiatry of Women and Children, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Hui Ding
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Yan-Ping Shu
- Department of Psychiatry of Women and Children, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Jing Li
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Xi-Zhao Chen
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Jia-Lin Li
- Medical Humanities College, Guizhou Medical University, Guiyang 550000, Guizhou Province, China
| | - Qin Lou
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
| | - Dai-Xing Wang
- Department of Radiology, The Second People’s Hospital of Guizhou Province, Guiyang 550000, Guizhou Province, China
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16
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Stengl M, Schneider AC. Contribution of membrane-associated oscillators to biological timing at different timescales. Front Physiol 2024; 14:1243455. [PMID: 38264332 PMCID: PMC10803594 DOI: 10.3389/fphys.2023.1243455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 12/12/2023] [Indexed: 01/25/2024] Open
Abstract
Environmental rhythms such as the daily light-dark cycle selected for endogenous clocks. These clocks predict regular environmental changes and provide the basis for well-timed adaptive homeostasis in physiology and behavior of organisms. Endogenous clocks are oscillators that are based on positive feedforward and negative feedback loops. They generate stable rhythms even under constant conditions. Since even weak interactions between oscillators allow for autonomous synchronization, coupling/synchronization of oscillators provides the basis of self-organized physiological timing. Amongst the most thoroughly researched clocks are the endogenous circadian clock neurons in mammals and insects. They comprise nuclear clockworks of transcriptional/translational feedback loops (TTFL) that generate ∼24 h rhythms in clock gene expression entrained to the environmental day-night cycle. It is generally assumed that this TTFL clockwork drives all circadian oscillations within and between clock cells, being the basis of any circadian rhythm in physiology and behavior of organisms. Instead of the current gene-based hierarchical clock model we provide here a systems view of timing. We suggest that a coupled system of autonomous TTFL and posttranslational feedback loop (PTFL) oscillators/clocks that run at multiple timescales governs adaptive, dynamic homeostasis of physiology and behavior. We focus on mammalian and insect neurons as endogenous oscillators at multiple timescales. We suggest that neuronal plasma membrane-associated signalosomes constitute specific autonomous PTFL clocks that generate localized but interlinked oscillations of membrane potential and intracellular messengers with specific endogenous frequencies. In each clock neuron multiscale interactions of TTFL and PTFL oscillators/clocks form a temporally structured oscillatory network with a common complex frequency-band comprising superimposed multiscale oscillations. Coupling between oscillator/clock neurons provides the next level of complexity of an oscillatory network. This systemic dynamic network of molecular and cellular oscillators/clocks is suggested to form the basis of any physiological homeostasis that cycles through dynamic homeostatic setpoints with a characteristic frequency-band as hallmark. We propose that mechanisms of homeostatic plasticity maintain the stability of these dynamic setpoints, whereas Hebbian plasticity enables switching between setpoints via coupling factors, like biogenic amines and/or neuropeptides. They reprogram the network to a new common frequency, a new dynamic setpoint. Our novel hypothesis is up for experimental challenge.
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Affiliation(s)
- Monika Stengl
- Department of Biology, Animal Physiology/Neuroethology, University of Kassel, Kassel, Germany
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17
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Skorucak J, Bölsterli BK, Storz S, Leach S, Schmitt B, Ramantani G, Huber R. Automated analysis of a large-scale paediatric dataset illustrates the interdependent relationship between epilepsy and sleep. Sci Rep 2023; 13:12882. [PMID: 37553387 PMCID: PMC10409812 DOI: 10.1038/s41598-023-39984-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 08/03/2023] [Indexed: 08/10/2023] Open
Abstract
Slow waves are an electrophysiological characteristic of non-rapid eye movement sleep and a marker of the restorative function of sleep. In certain pathological conditions, such as different types of epilepsy, slow-wave sleep is affected by epileptiform discharges forming so-called "spike-waves". Previous evidence shows that the overnight change in slope of slow waves during sleep is impaired under these conditions. However, these past studies were performed in a small number of patients, considering only short segments of the recording night. Here, we screened a clinical data set of 39'179 pediatric EEG recordings acquired in the past 25 years (1994-2019) at the University Children's Hospital Zurich and identified 413 recordings of interest. We applied an automated approach based on machine learning to investigate the relationship between sleep and epileptic spikes in this large-scale data set. Our findings show that the overnight change in the slope of slow waves was correlated with the spike-wave index, indicating that the impairment of the net reduction in synaptic strength during sleep is spike dependent.
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Affiliation(s)
- Jelena Skorucak
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Bigna K Bölsterli
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Pediatric Neurology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland
| | - Sarah Storz
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Sven Leach
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Bernhard Schmitt
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Georgia Ramantani
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Reto Huber
- Child Development Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
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18
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Perversi F, Costa C, Labate A, Lattanzi S, Liguori C, Maschio M, Meletti S, Nobili L, Operto FF, Romigi A, Russo E, Di Bonaventura C. The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy. Front Neurol 2023; 14:1182304. [PMID: 37483446 PMCID: PMC10359664 DOI: 10.3389/fneur.2023.1182304] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 06/07/2023] [Indexed: 07/25/2023] Open
Abstract
Glutamate is the brain's main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies-especially those produced from 2017 onwards-on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists.
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Affiliation(s)
| | - Cinzia Costa
- Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
- Neurological Clinic, S. Maria Della Misericordia Hospital, Perugia, Italy
| | - Angelo Labate
- Neurophysiopatology and Movement Disorders Clinic, University of Messina, Messina, Italy
| | - Simona Lattanzi
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy
| | - Claudio Liguori
- Department of Systems Medicine, University of Rome ‘Tor Vergata”, Rome, Italy
- Epilepsy Center, Neurology Unit, University Hospital “Tor Vergata”, Rome, Italy
| | - Marta Maschio
- Center for Tumor-Related Epilepsy, UOSD Neuro-Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Stefano Meletti
- Neurology Department, University Hospital of Modena, Modena, Italy
- Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio-Emilia, Modena, Italy
| | - Lino Nobili
- Child Neuropsychiatry Unit, IRCCS Istituto G. Gaslini, Genova, Italy
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Child and Maternal Health (DINOGMI), University of Genova, Genova, Italy
| | - Francesca Felicia Operto
- Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy
- Department of Science of Health, School of Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Andrea Romigi
- Sleep Medicine Center, Neurological Mediterranean Institute IRCCS Neuromed, Pozzilli, Italy
- Psychology Faculty, International Telematic University Uninettuno, Rome, Italy
| | - Emilio Russo
- Department of Science of Health, School of Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Carlo Di Bonaventura
- Epilepsy Unit, Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
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Brodt S, Inostroza M, Niethard N, Born J. Sleep-A brain-state serving systems memory consolidation. Neuron 2023; 111:1050-1075. [PMID: 37023710 DOI: 10.1016/j.neuron.2023.03.005] [Citation(s) in RCA: 86] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/23/2023] [Accepted: 03/06/2023] [Indexed: 04/08/2023]
Abstract
Although long-term memory consolidation is supported by sleep, it is unclear how it differs from that during wakefulness. Our review, focusing on recent advances in the field, identifies the repeated replay of neuronal firing patterns as a basic mechanism triggering consolidation during sleep and wakefulness. During sleep, memory replay occurs during slow-wave sleep (SWS) in hippocampal assemblies together with ripples, thalamic spindles, neocortical slow oscillations, and noradrenergic activity. Here, hippocampal replay likely favors the transformation of hippocampus-dependent episodic memory into schema-like neocortical memory. REM sleep following SWS might balance local synaptic rescaling accompanying memory transformation with a sleep-dependent homeostatic process of global synaptic renormalization. Sleep-dependent memory transformation is intensified during early development despite the immaturity of the hippocampus. Overall, beyond its greater efficacy, sleep consolidation differs from wake consolidation mainly in that it is supported, rather than impaired, by spontaneous hippocampal replay activity possibly gating memory formation in neocortex.
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Affiliation(s)
- Svenja Brodt
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany; Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany
| | - Marion Inostroza
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany
| | - Niels Niethard
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany
| | - Jan Born
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany; Werner Reichert Center for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
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20
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Issa NP, Nunn KC, Wu S, Haider HA, Tao JX. Putative roles for homeostatic plasticity in epileptogenesis. Epilepsia 2023; 64:539-552. [PMID: 36617338 PMCID: PMC10015501 DOI: 10.1111/epi.17500] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 01/04/2023] [Accepted: 01/05/2023] [Indexed: 01/09/2023]
Abstract
Homeostatic plasticity allows neural circuits to maintain an average activity level while preserving the ability to learn new associations and efficiently transmit information. This dynamic process usually protects the brain from excessive activity, like seizures. However, in certain contexts, homeostatic plasticity might produce seizures, either in response to an acute provocation or more chronically as a driver of epileptogenesis. Here, we review three seizure conditions in which homeostatic plasticity likely plays an important role: acute drug withdrawal seizures, posttraumatic or disconnection epilepsy, and cyclic seizures. Identifying the homeostatic mechanisms active at different stages of development and in different circuits could allow better targeting of therapies, including determining when neuromodulation might be most effective, proposing ways to prevent epileptogenesis, and determining how to disrupt the cycle of recurring seizure clusters.
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Affiliation(s)
- Naoum P. Issa
- Comprehensive Epilepsy Center, Department of Neurology, 5841 S. Maryland Ave., MC 2030, University of Chicago, Chicago, IL 60637
| | | | - Shasha Wu
- Comprehensive Epilepsy Center, Department of Neurology, 5841 S. Maryland Ave., MC 2030, University of Chicago, Chicago, IL 60637
| | - Hiba A. Haider
- Comprehensive Epilepsy Center, Department of Neurology, 5841 S. Maryland Ave., MC 2030, University of Chicago, Chicago, IL 60637
| | - James X. Tao
- Comprehensive Epilepsy Center, Department of Neurology, 5841 S. Maryland Ave., MC 2030, University of Chicago, Chicago, IL 60637
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21
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Giri B, Kaya U, Maboudi K, Abel T, Diba K. Sleep loss diminishes hippocampal reactivation and replay. RESEARCH SQUARE 2023:rs.3.rs-2540186. [PMID: 36824950 PMCID: PMC9949250 DOI: 10.21203/rs.3.rs-2540186/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
Memories benefit from sleep, and sleep loss immediately following learning has a negative impact on subsequent memory storage. Several prominent hypotheses ascribe a central role to hippocampal sharp-wave ripples (SWRs), and the concurrent reactivation and replay of neuronal patterns from waking experience, in the offline memory consolidation process that occurs during sleep. However, little is known about how SWRs, reactivation, and replay are affected when animals are subjected to sleep deprivation. We performed long duration (~12 h), high-density silicon probe recordings from rat hippocampal CA1 neurons, in animals that were either sleeping or sleep deprived following exposure to a novel maze environment. We found that SWRs showed a sustained rate of activity during sleep deprivation, similar to or higher than in natural sleep, but with decreased amplitudes for the sharp-waves combined with higher frequencies for the ripples. Furthermore, while hippocampal pyramidal cells showed a log-normal distribution of firing rates during sleep, these distributions were negatively skewed with a higher mean firing rate in both pyramidal cells and interneurons during sleep deprivation. During SWRs, however, firing rates were remarkably similar between both groups. Despite the abundant quantity of SWRs and the robust firing activity during these events in both groups, we found that reactivation of neurons was either completely abolished or significantly diminished during sleep deprivation compared to sleep. Interestingly, reactivation partially rebounded upon recovery sleep, but failed to reach the levels characteristic of natural sleep. Similarly, the number of replays were significantly lower during sleep deprivation and recovery sleep compared to natural sleep. These results provide a network-level account for the negative impact of sleep loss on hippocampal function and demonstrate that sleep loss impacts memory storage by causing a dissociation between the amount of SWRs and the replays and reactivations that take place during these events.
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Affiliation(s)
- Bapun Giri
- Dept of Anesthesiology and Neuroscience Graduate Program, 1150 W Medical Center Dr, University of Michigan Medical School, Ann Arbor, MI 48109
- Dept of Psychology, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, WI 53201
| | - Utku Kaya
- Dept of Anesthesiology and Neuroscience Graduate Program, 1150 W Medical Center Dr, University of Michigan Medical School, Ann Arbor, MI 48109
| | - Kourosh Maboudi
- Dept of Anesthesiology and Neuroscience Graduate Program, 1150 W Medical Center Dr, University of Michigan Medical School, Ann Arbor, MI 48109
- Dept of Psychology, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, WI 53201
| | - Ted Abel
- Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
| | - Kamran Diba
- Dept of Anesthesiology and Neuroscience Graduate Program, 1150 W Medical Center Dr, University of Michigan Medical School, Ann Arbor, MI 48109
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22
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Brain Waste Removal System and Sleep: Photobiomodulation as an Innovative Strategy for Night Therapy of Brain Diseases. Int J Mol Sci 2023; 24:ijms24043221. [PMID: 36834631 PMCID: PMC9965491 DOI: 10.3390/ijms24043221] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/28/2023] [Accepted: 02/02/2023] [Indexed: 02/10/2023] Open
Abstract
Emerging evidence suggests that an important function of the sleeping brain is the removal of wastes and toxins from the central nervous system (CNS) due to the activation of the brain waste removal system (BWRS). The meningeal lymphatic vessels (MLVs) are an important part of the BWRS. A decrease in MLV function is associated with Alzheimer's and Parkinson's diseases, intracranial hemorrhages, brain tumors and trauma. Since the BWRS is activated during sleep, a new idea is now being actively discussed in the scientific community: night stimulation of the BWRS might be an innovative and promising strategy for neurorehabilitation medicine. This review highlights new trends in photobiomodulation of the BWRS/MLVs during deep sleep as a breakthrough technology for the effective removal of wastes and unnecessary compounds from the brain in order to increase the neuroprotection of the CNS as well as to prevent or delay various brain diseases.
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Mader EC, Mader ACL, Singh P. Insufficient Sleep Syndrome: A Blind Spot in Our Vision of Healthy Sleep. Cureus 2022; 14:e30928. [PMID: 36337802 PMCID: PMC9626376 DOI: 10.7759/cureus.30928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2022] [Indexed: 11/05/2022] Open
Abstract
Chronic sleep deficiency (CSD) poses a threat to physical health, mental well-being, and social functioning. The concept of behaviorally induced CSD has not changed much since it was first introduced four decades ago. Behaviorally induced CSD is currently referred to as insufficient sleep syndrome (ISS). In the latest edition of the International Classification of Sleep Disorders (ICSD-3, 2014), ISS is considered a disorder of central hypersomnolence with diagnostic codes ICD-9-CM 307.44 and ICD-10-CM F51.12. In this review, we will describe the biological importance of sleep, the ramifications of CSD on the individual and society, the nosological status and diagnostic features of ISS, and the apparent lack of attention to ISS in contemporary medical practice and public health programs. The last three decades have seen a global rise in voluntary sleep curtailment such that ISS may already be the leading cause of CSD, not only in adults but also in school-aged children and adolescents. Acknowledging ISS as a public health priority is a necessary first step in our response to the global threat of CSD and CSD-related health consequences. It is only by confronting ISS directly that we can hope to develop and implement effective educational and advocacy programs, along with more responsible public health policies and regulations.
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Affiliation(s)
- Edward C Mader
- Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, USA
| | | | - Prachi Singh
- Sleep and Cardiometabolic Health Laboratories, Louisiana State University Pennington Biomedical Research Center, Baton Rouge, USA
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24
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Borbély A. The two-process model of sleep regulation: Beginnings and outlook. J Sleep Res 2022; 31:e13598. [PMID: 35502706 PMCID: PMC9540767 DOI: 10.1111/jsr.13598] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 01/10/2023]
Abstract
The two-process model serves as a major conceptual framework in sleep science. Although dating back more than four decades, it has not lost its relevance for research today. Retracing its origins, I describe how animal experiments aimed at exploring the oscillators driving the circadian sleep-wake rhythm led to the recognition of gradients of sleep states within the daily sleep period. Advances in signal analysis revealed that the level of slow-wave activity in non-rapid eye movement sleep electroencephalogram is high at the beginning of the 12-light period and then declines. After sleep deprivation, the level of slow-wave activity is enhanced. By scheduling recovery sleep to the animal's activity period, the conflict between the sleep-wake-dependent and the circadian influence resulted in a two-stage recovery pattern. These experiments provided the basis for the first version of the two-process model. Sleep deprivation experiments in humans showed that the decline of slow-wave activity during sleep is exponential. The two-process model posits that a sleep-wake-dependent homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C). At present, homeostatic and circadian facets of sleep regulation are being investigated at the synaptic level as well as in the transcriptome and proteome domains. The notion of sleep has been extended from a global phenomenon to local representations, while the master circadian pacemaker has been supplemented by multiple peripheral oscillators. The original interpretation that the emergence of sleep may be viewed as an escape from the rigid control imposed by the circadian pacemaker is still upheld.
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Affiliation(s)
- Alexander Borbély
- Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
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25
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Editorial - The Making of Memories. Semin Cell Dev Biol 2022; 125:66-67. [PMID: 35135720 DOI: 10.1016/j.semcdb.2022.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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26
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Rapid-acting antidepressants and the circadian clock. Neuropsychopharmacology 2022; 47:805-816. [PMID: 34837078 PMCID: PMC8626287 DOI: 10.1038/s41386-021-01241-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 09/20/2021] [Accepted: 11/08/2021] [Indexed: 12/13/2022]
Abstract
A growing number of epidemiological and experimental studies has established that circadian disruption is strongly associated with psychiatric disorders, including major depressive disorder (MDD). This association is becoming increasingly relevant considering that modern lifestyles, social zeitgebers (time cues) and genetic variants contribute to disrupting circadian rhythms that may lead to psychiatric disorders. Circadian abnormalities associated with MDD include dysregulated rhythms of sleep, temperature, hormonal secretions, and mood which are modulated by the molecular clock. Rapid-acting antidepressants such as subanesthetic ketamine and sleep deprivation therapy can improve symptoms within 24 h in a subset of depressed patients, in striking contrast to conventional treatments, which generally require weeks for a full clinical response. Importantly, animal data show that sleep deprivation and ketamine have overlapping effects on clock gene expression. Furthermore, emerging data implicate the circadian system as a critical component involved in rapid antidepressant responses via several intracellular signaling pathways such as GSK3β, mTOR, MAPK, and NOTCH to initiate synaptic plasticity. Future research on the relationship between depression and the circadian clock may contribute to the development of novel therapeutic strategies for depression-like symptoms. In this review we summarize recent evidence describing: (1) how the circadian clock is implicated in depression, (2) how clock genes may contribute to fast-acting antidepressants, and (3) the mechanistic links between the clock genes driving circadian rhythms and neuroplasticity.
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27
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Loschky SS, Spano GM, Marshall W, Schroeder A, Nemec KM, Schiereck SS, de Vivo L, Bellesi M, Banningh SW, Tononi G, Cirelli C. Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum. eLife 2022; 11:84199. [PMID: 36576248 PMCID: PMC9797193 DOI: 10.7554/elife.84199] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/18/2022] [Indexed: 12/29/2022] Open
Abstract
Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain's ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here, we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7000 spines and their parallel fiber synapses in the mouse posterior vermis. This analysis was done in mice whose cortical and hippocampal synapses were previously measured, revealing that average synaptic size was lower after sleep compared to wake with no major changes in synapse number. Here, instead, we find that while the average size of parallel fiber synapses does not change, the number of branched synapses is reduced in half after sleep compared to after wake, corresponding to ~16% of all spines after wake and ~8% after sleep. Branched synapses are harbored by two or more spines sharing the same neck and, as also shown here, are almost always contacted by different parallel fibers. These findings suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective in driving Purkinje cells to fire. By contrast, sleep may promote the off-line pruning of branched synapses that were formed due to spurious coincidences.
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Affiliation(s)
- Sophia S Loschky
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | | | - William Marshall
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States,Department of Mathematics and Statistics, Brock UniversitySt. CatharinesCanada
| | - Andrea Schroeder
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | - Kelsey Marie Nemec
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | | | - Luisa de Vivo
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | - Michele Bellesi
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | | | - Giulio Tononi
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
| | - Chiara Cirelli
- Department of Psychiatry, University of Wisconsin-MadisonMadisonUnited States
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28
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Ruch S, Alain Züst M, Henke K. Sleep-learning impairs subsequent awake-learning. Neurobiol Learn Mem 2021; 187:107569. [PMID: 34863922 DOI: 10.1016/j.nlm.2021.107569] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 09/21/2021] [Accepted: 11/26/2021] [Indexed: 01/11/2023]
Abstract
Although we can learn new information while asleep, we usually cannot consciously remember the sleep-formed memories - presumably because learning occurred in an unconscious state. Here, we ask whether sleep-learning expedites the subsequent awake-learning of the same information. To answer this question, we reanalyzed data (Züst et al., 2019, Curr Biol) from napping participants, who learned new semantic associations between pseudowords and translation-words (guga-ship) while in slow-wave sleep. They retrieved sleep-formed associations unconsciously on an implicit memory test following awakening. Then, participants took five runs of paired-associative learning to probe carry-over effects of sleep-learning on awake-learning. Surprisingly, sleep-learning diminished awake-learning when participants learned semantic associations that were congruent to sleep-learned associations (guga-boat). Yet, learning associations that conflicted with sleep-learned associations (guga-coin) was unimpaired relative to learning new associations (resun-table; baseline). We speculate that the impeded wake-learning originated in a deficient synaptic downscaling and resulting synaptic saturation in neurons that were activated during both sleep-learning and awake-learning.
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Affiliation(s)
- Simon Ruch
- Cognitive Neuroscience of Memory and Consciousness, Institute of Psychology, University of Bern, Fabrikstrasse 8, 3012 Bern, Switzerland.
| | - Marc Alain Züst
- Cognitive Neuroscience of Memory and Consciousness, Institute of Psychology, University of Bern, Fabrikstrasse 8, 3012 Bern, Switzerland
| | - Katharina Henke
- Cognitive Neuroscience of Memory and Consciousness, Institute of Psychology, University of Bern, Fabrikstrasse 8, 3012 Bern, Switzerland
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29
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Franks NP, Wisden W. The inescapable drive to sleep: Overlapping mechanisms of sleep and sedation. Science 2021; 374:556-559. [PMID: 34709918 DOI: 10.1126/science.abi8372] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Nicholas P Franks
- Department of Life Sciences and UK Dementia Research Institute, Imperial College London, London SW7 2AZ, UK
| | - William Wisden
- Department of Life Sciences and UK Dementia Research Institute, Imperial College London, London SW7 2AZ, UK
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30
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Computational Modeling of Information Propagation during the Sleep–Waking Cycle. BIOLOGY 2021; 10:biology10100945. [PMID: 34681044 PMCID: PMC8533346 DOI: 10.3390/biology10100945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/09/2021] [Accepted: 09/16/2021] [Indexed: 11/16/2022]
Abstract
Simple Summary During the deep phases of sleep we do not normally wake up by a thunder, but we nevertheless notice it when awake. The exact same sound gets to our ears and cortex through the thalamus and still, it triggers two very different responses. There is growing experimental evidence that these two states of the brain—sleep and wakefulness—distribute sensory information in different ways across the cortex. In particular, during sleep, neuronal responses remain local and do not spread out across distant synaptically connected regions. On the contrary, during wakefulness, stimuli are able to elicit a wider spatial response. We have used a computational model of coupled cortical columns to study how these two propagation modes arise. Moreover, the transition from sleep-like to waking-like dynamics occurs in agreement with the synaptic homeostasis hypothesis and only requires the increase of excitatory conductances. We have found that, in order to reproduce the aforementioned observations, this parameter change has to be selectively applied: synaptic conductances between distinct columns have to be potentiated over local ones. Abstract Non-threatening familiar sounds can go unnoticed during sleep despite the fact that they enter our brain by exciting the auditory nerves. Extracellular cortical recordings in the primary auditory cortex of rodents show that an increase in firing rate in response to pure tones during deep phases of sleep is comparable to those evoked during wakefulness. This result challenges the hypothesis that during sleep cortical responses are weakened through thalamic gating. An alternative explanation comes from the observation that the spatiotemporal spread of the evoked activity by transcranial magnetic stimulation in humans is reduced during non-rapid eye movement (NREM) sleep as compared to the wider propagation to other cortical regions during wakefulness. Thus, cortical responses during NREM sleep remain local and the stimulus only reaches nearby neuronal populations. We aim at understanding how this behavior emerges in the brain as it spontaneously shifts between NREM sleep and wakefulness. To do so, we have used a computational neural-mass model to reproduce the dynamics of the sensory auditory cortex and corresponding local field potentials in these two brain states. Following the synaptic homeostasis hypothesis, an increase in a single parameter, namely the excitatory conductance g¯AMPA, allows us to place the model from NREM sleep into wakefulness. In agreement with the experimental results, the endogenous dynamics during NREM sleep produces a comparable, even higher, response to excitatory inputs to the ones during wakefulness. We have extended the model to two bidirectionally connected cortical columns and have quantified the propagation of an excitatory input as a function of their coupling. We have found that the general increase in all conductances of the cortical excitatory synapses that drive the system from NREM sleep to wakefulness does not boost the effective connectivity between cortical columns. Instead, it is the inter-/intra-conductance ratio of cortical excitatory synapses that should raise to facilitate information propagation across the brain.
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31
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Miyamoto D, Marshall W, Tononi G, Cirelli C. Net decrease in spine-surface GluA1-containing AMPA receptors after post-learning sleep in the adult mouse cortex. Nat Commun 2021; 12:2881. [PMID: 34001888 PMCID: PMC8129120 DOI: 10.1038/s41467-021-23156-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 04/12/2021] [Indexed: 02/03/2023] Open
Abstract
The mechanisms by which sleep benefits learning and memory remain unclear. Sleep may further strengthen the synapses potentiated by learning or promote broad synaptic weakening while protecting the newly potentiated synapses. We tested these ideas by combining a motor task whose consolidation is sleep-dependent, a marker of synaptic AMPA receptor plasticity, and repeated two-photon imaging to track hundreds of spines in vivo with single spine resolution. In mouse motor cortex, sleep leads to an overall net decrease in spine-surface GluA1-containing AMPA receptors, both before and after learning. Molecular changes in single spines during post-learning sleep are correlated with changes in performance after sleep. The spines in which learning leads to the largest increase in GluA1 expression have a relative advantage after post-learning sleep compared to sleep deprivation, because sleep weakens all remaining spines. These results are obtained in adult mice, showing that sleep-dependent synaptic down-selection also benefits the mature brain.
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Affiliation(s)
- Daisuke Miyamoto
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
- University of Toyama, Toyama, Japan
| | - William Marshall
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
- Department of Mathematics and Statistics, Brock University, St. Catharines, ON, Canada
| | - Giulio Tononi
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
| | - Chiara Cirelli
- Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
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