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Optogenetic dissection of hypothalamic regulation of sleep-wake states

English title Optogenetic dissection of hypothalamic regulation of sleep-wake states
Applicant Adamantidis Antoine
Number 156156
Funding scheme Project funding (Div. I-III)
Research institution Universitätsklinik für Neurologie Inselspital Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2015 - 31.12.2018
Approved amount 454'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Physiology : other topics

Keywords (6)

Wake; Sleep; Optogenetics; Neural circuits; Thalamus; Hypothalamus

Lay Summary (French)

Lead
Identification d'un nouveau circuit de l'eveil.
Lay summary

Le sommeil est un besoin biologique essentiel pour la survie des vertébrés supérieurs et des états de veille-sommeil ont egalement été identifiés chez les vertébrés inférieurs. Alors que les fonctions du sommeil sont encore un sujet de débat et peuvent inclure la consolidation mnesique et la plasticité cerebrale, les mechanismes cerebraux contrôlant le cycle veille-sommeil restent mal compris et font encore l'objet de nombreuses études. La sucession des differents etats de vigilance (eveil-sommeil leger-sommeil profond) resulte de l'activite neuronales au sein d’aires cerebrales distinctes. Chez l'homme, des troubles bénins de cet équilibre peuvent avoir des conséquences dramatiques, comme par exemple, narcolepsie, insomnie), déséquilibre hormonal souvent suivi par l'obésité, les déficits de l'attention et les performances cognitives, et ont été liés à l'humeur et les troubles cardiovasculaires. Le manque de traitements pharmacologiques efficaces sans effets secondaires majeurs souligne la nécessité d'une meilleure compréhension des mécanismes de base de l'induction du sommeil et de maintien du sommeil.

A l’heure actuelle, la connectivite et la dynamique de les differents circuits veille-sommeil restent mal comprises. neanmoins leurs connections. Au cours de ce projet, nous combinerons les approches moléculaires, cellulaires et comportementales pour identifier les circuits neuronaux entre l’hypothalamus et le thalamus qui controlent l’apparition de phases d’éveil. Nous utiliserons des souris genetiquement modifies qui represent un modele animal ideal pour ce type d’etude experimentale. A plus long terme, notre travail devrait permettre non seulement d’identifier les mechanisms cerebraux de l’eveil, mais egalement de l’attention, ainsi que leur role dans l’insomnie.

 

Direct link to Lay Summary Last update: 09.12.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Sleep as a model to understand neuroplasticity and recovery after stroke: Observational, perturbational and interventional approaches
Mensen Armand, Pigorini Andrea, Facchin Laura, Schöne Cornelia, D'Ambrosio Sasha, Jendoubi Jasmine, Jaramillo Valeria, Chiffi Kathrin, Eberhard-Moscicka Aleksandra K., Sarasso Simone, Adamantidis Antoine, Müri René M., Huber Reto, Massimini Marcello, Bassetti Claudio (2019), Sleep as a model to understand neuroplasticity and recovery after stroke: Observational, perturbational and interventional approaches, in Journal of Neuroscience Methods, 313, 37-43.
Sleep-Wake Cycling and Energy Conservation: Role of Hypocretin and the Lateral Hypothalamus in Dynamic State-Dependent Resource Optimization
Latifi Blerina, Adamantidis Antoine, Bassetti Claudio, Schmidt Markus H. (2018), Sleep-Wake Cycling and Energy Conservation: Role of Hypocretin and the Lateral Hypothalamus in Dynamic State-Dependent Resource Optimization, in Frontiers in Neurology, 9, 790-795.
Sleep-wake control and the thalamus
Gent Thomas C, Bassetti Claudio LA, Adamantidis Antoine R (2018), Sleep-wake control and the thalamus, in Current Opinion in Neurobiology, 52, 188-197.
Melanin-concentrating hormone and sleep
Ferreira Jozelia Gomes Pacheco, Bittencourt Jackson Cioni, Adamantidis Antoine (2017), Melanin-concentrating hormone and sleep, in Current Opinion in Neurobiology, 44, 152-158.
REM sleep and memory
Boyce Richard, Williams Sylvain, Adamantidis Antoine (2017), REM sleep and memory, in Current Opinion in Neurobiology, 44, 167-177.
Monoaminergic control of brain states and sensory processing: Existing knowledge and recent insights obtained with optogenetics
Lőrincz Magor L., Adamantidis Antoine R. (2017), Monoaminergic control of brain states and sensory processing: Existing knowledge and recent insights obtained with optogenetics, in Progress in Neurobiology, 151, 237-253.
Sleep & metabolism: The multitasking ability of lateral hypothalamic inhibitory circuitries
Herrera Carolina Gutierrez, Ponomarenko Alexey, Korotkova Tatiana, Burdakov Denis, Adamantidis Antoine (2017), Sleep & metabolism: The multitasking ability of lateral hypothalamic inhibitory circuitries, in Frontiers in Neuroendocrinology, 44, 27-34.
Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation
Boyce R., Glasgow S. D., Williams S., Adamantidis A. (2016), Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation, in Science, 352(6287), 812-816.
Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade
Bassetti C. L., Ferini-Strambi L., Brown S., Adamantidis A., Benedetti F., Bruni O., Cajochen C., Dolenc-Groselj L., Ferri R., Gais S., Huber R., Khatami R., Lammers G. J., Luppi P. H., Manconi M., Nissen C., Nobili L., Peigneux P., Pollmächer T., Randerath W., Riemann D., Santamaria J., Schindler K., Tafti M., et al. (2015), Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade, in European Journal of Neurology, 22(10), 1337-1354.
Optogenetics: 10 years after ChR2 in neurons—views from the community
Adamantidis Antoine, Arber Silvia, Bains Jaideep S, Bamberg Ernst, Bonci Antonello, Buzsáki György, Cardin Jessica A, Costa Rui M, Dan Yang, Goda Yukiko, Graybiel Ann M, Häusser Michael, Hegemann Peter, Huguenard John R, Insel Thomas R, Janak Patricia H, Johnston Daniel, Josselyn Sheena A, Koch Christof, Kreitzer Anatol C, Lüscher Christian, Malenka Robert C, Miesenböck Gero, Nagel Georg, et al. (2015), Optogenetics: 10 years after ChR2 in neurons—views from the community, in Nature Neuroscience, 18(9), 1202-1212.

Collaboration

Group / person Country
Types of collaboration
Prof S. Williams Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof Burdakov Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof Marcello Massimini Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. T. Korotkova Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. C. Bassetti Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
talk at Uni Fribourg Individual talk Thalamic dual-modulation of sleep and wakefulness 12.12.2018 Fribourg, Switzerland Adamantidis Antoine;
Talk at University of Lausanne Individual talk Dissection of sleep circuits and functions in the brain 26.11.2018 Lausanne, Switzerland Adamantidis Antoine;
Talk at University of Copenhagen Individual talk Thalamic dual-modulation of sleep and wakefulness 21.11.2018 Copenhagen, Denmark Adamantidis Antoine;
talk at University of Aarhus Individual talk Thalamic dual-modulation of sleep and wakefulness 20.11.2018 Aarhus, Denmark Adamantidis Antoine;
World Life Science Conference, Frontiers in Sleep Studies Talk given at a conference Dissection of sleep circuits and functions in the brain 27.10.2018 Peking, China Adamantidis Antoine;
24rd congress of the european sleep research society Poster Reactivation of hypothalamic inhibitory neurons during REM sleep consolidates appetite 25.09.2018 Basel, Switzerland Oesch Lukas;
7th Symposium on narcolepsy Talk given at a conference Thalamic dual control of sleep and wakefulness 09.09.2018 Boston, United States of America Adamantidis Antoine;
11th FENS Forum of Neuroscience Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 07.07.2018 Berlin, Germany Adamantidis Antoine;
11th FENS forum Poster Reactivation of hypothalamic inhibitory neurons during REM sleep consolidates appetite 07.07.2018 Berlin, Germany Oesch Lukas;
Giessbach meeting: "Cellular and molecular neurobiology of mental disease" Talk given at a conference Reactivation of hypothalamic inhibitory neurons during REM sleep stabilizes appetite 25.05.2018 Giessbach, Switzerland Oesch Lukas;
talk at University of Groningen Individual talk Optogenetic dissection of sleep circuits and function(s) 20.04.2018 Groningen, Netherlands Adamantidis Antoine;
Gordon research Seminar: "Sleep regulation and function" Poster Reactivation of hypothalamic inhibitory neurons during REM sleep consolidates appetite 17.03.2018 Galveston, United States of America Oesch Lukas;
talk at European Institute for theortical Neuroscience (EITN) Individual talk Thalamic dual control of sleep and wakefulness 01.03.2018 Paris, France Adamantidis Antoine;
Gordon Research Conference “Thalamocortical Interactions” Talk given at a conference Dissection of sleep circuits and functions in the brain 18.02.2018 Lucca, Italy Adamantidis Antoine;
20th annual meeting of the swiss society for neuroscience Poster Reactivation of hypothalamic inhibitory neurons during REM sleep consolidates appetite 09.02.2018 Zürich, Switzerland Oesch Lukas;
GCB symposium 2018 Talk given at a conference The neurodiet - dream your weight away 01.02.2018 Bern, Switzerland Oesch Lukas;
talk at Weizmann Institute Individual talk Optogenetic dissection of sleep circuits and function(s) 03.01.2018 Tel Aviv, Israel Adamantidis Antoine;
5th WPI-IIIS Symposium Talk given at a conference Thalamic dual control of sleep and wakefulness 14.12.2017 Tokio, Japan Adamantidis Antoine;
NeuralNet Symposium Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 22.11.2017 Strasbourg, France Adamantidis Antoine;
talk at University of Warwick Individual talk Dissection of sleep circuits and functions in the brain 16.11.2017 Coventry, Great Britain and Northern Ireland Adamantidis Antoine;
3rd ZEN symposium Talk given at a conference Reactivation of hypothalamic inhibitory neurons during REM sleep consolidates appetite 27.10.2017 Bern, Switzerland Oesch Lukas;
1st World Sleep Federation conference Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 07.10.2017 Prague, Czech Republic Adamantidis Antoine;
FESN regional Meeting Talk given at a conference Thalamic dual control of sleep and wakefulness 20.09.2017 Pécs, Hungary Adamantidis Antoine;
FENS regional meeting Poster REM sleep reactivation of lateral hypothalamus neurons associated with goal-oriented behaviors conditions food intake during wakefulness 20.09.2017 Pécs, Hungary Oesch Lukas;
Neuromodulation NM2 Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 18.09.2017 Lausanne, Switzerland Adamantidis Antoine;
12th clinical neuroscience Bern meeting Poster REM sleep reactivation of lateral hypothalamus neurons associated with goal-oriented behaviors conditions food intake during wakefulness 08.09.2017 Bern, Switzerland Oesch Lukas;
European Academy of Neurology Talk given at a conference Thalamic dual control of sleep and wakefulness 24.07.2017 Amsterdam, Netherlands Adamantidis Antoine;
Japanese Neuroscience Society Talk given at a conference Thalamic dual control of sleep and wakefulness 20.07.2017 Chiba, Japan Adamantidis Antoine;
Gordon Research Conference “Inhibition in the CNS Talk given at a conference Dissection of sleep circuits and functions in the brain 25.06.2017 Les Diablerets, Switzerland Adamantidis Antoine;
Swiss Society for Sleep Research, Sleep Medicine and Chronobiology Talk given at a conference Thalamic dual control of sleep and wakefulness 11.05.2017 Lugano, Switzerland Adamantidis Antoine;
talk at Edinburgh, Roslin Institute Individual talk Dissection of sleep circuits and functions in the brain 08.05.2017 Edinbourgh, Great Britain and Northern Ireland Adamantidis Antoine;
12th Meeting of the German Neuroscience Society Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 22.03.2017 Göttingen, Germany Adamantidis Antoine;
5th Benesco winter research meeting Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 09.03.2017 Wengen, Switzerland Oesch Lukas;
19th annual meeting of the swiss society for neuroscience Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 27.01.2017 Basel, Switzerland Oesch Lukas;
Brain mind institute symposium: "Connectivity and plasticity of neural circuits" Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 12.12.2016 Lausanne, Switzerland Oesch Lukas;
IIIS Lecture Individual talk Thalamic dual-modulation of sleep and wakefulness 08.12.2016 Tsukuba, Japan Adamantidis Antoine;
4th Bordeaux Neurocampus Conference Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 28.09.2016 Bordeaux, France Adamantidis Antoine;
23rd congress of the european sleep research society Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 13.09.2016 Bologna, Italy Oesch Lukas;
Sleep-Circadian Oxford Summerschool Talk given at a conference Dissection of sleep circuits and functions in the brain 01.08.2016 Oxford, Great Britain and Northern Ireland Adamantidis Antoine;
Conférance Jaques Monod: "Optical imaging of brain connectivity: from synapses to networks in action Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 13.06.2016 Roscoff, France Oesch Lukas;
Hellenic Sleep Research Society Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 28.04.2016 Athen, Greece Adamantidis Antoine;
FENS brain conference: "New approaches to imaging neurons and neural circuts" Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 17.04.2016 Rungstedgaard, Denmark Oesch Lukas;
18th International Neuroscience Winter Conference Talk given at a conference Thalamic dual control of sleep and wakefulness 02.04.2016 Sölden, Austria Adamantidis Antoine;
4th Benesco winter research meeting Poster Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 10.03.2016 Wengen, Switzerland Oesch Lukas;
Societe Francaise de Recherche sur le Sommeil Talk given at a conference Thalamic dual-modulation of sleep and wakefulness 18.11.2015 Nantes, France Adamantidis Antoine;
7th World Sleep Federation Talk given at a conference Dissection of sleep circuits and functions in the brain 31.10.2015 Istanbul, Turkey Adamantidis Antoine;
45th Society for Neurosciences Talk given at a conference Thalamic dual control of sleep and wakefulness 17.10.2015 Chicago, United States of America Adamantidis Antoine;
Brain & Brain PET Conference 2015 Talk given at a conference Dissection of sleep circuits and functions in the brain 27.06.2015 Vancouver, Canada Adamantidis Antoine;
6th World Association of Sleep Medicine Congress Talk given at a conference Optogenetic dissection of sleep circuits and function(s) 21.03.2015 Seoul, Korean Republic (South Korea) Adamantidis Antoine;


Awards

Title Year
European Research Council - ERC Consolidator Grant 2017
FENS travel grant FENS regional meeting 2017
Pfizer Research Prize, Switzerland 2017
Poster Award - Clinical Neuroscience Bern 2017
Poster price 12th clinical neuroscience Bern meeting 2017
FENS Travel Grant: FENS brain conference: "New approaches to imaging neurons and neural circuits" Title: Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 2016
SSSSC travel grant 23rd congress of the european sleep research society Title: Encoding of food intake and arousal by GABAergic neurons in the lateral hypothalamus 2016

Abstract

Sleep is a primary and essential biological need for higher vertebrates and sleep-like states have been demonstrated in lower vertebrates. While the functions of sleep are still a matter of debate and may include memory consolidation, metabolism clearance and brain plasticity, the basic neurobiological mechanisms controlling sleep-wake state transitions and maintenance remain largely unknown. The goal of this research proposal is to better understand the wiring, dynamics and plasticity of sleep-wake circuits in the brain.Our hypothesis is that a subpopulation LHGABA neurons promotes wakefulness by inhibition of RTN cells, which in turn, disinhibit thalamo-cortical loops. This feed-forward inhibitory circuit may represent a novel arousal circuit of the mammalian brain. To test this hypothesis, we divided our experimental strategy into three specific aims, including 1) Characterize the anatomical and functional LHGABA -> RTN wiring (Year 1); 2) Study the behavioral consequences of LHGABA -> RTN optogenetic activation on sleep-to-wake transitions (Years 1-2) and 3) Study the modulatory action of LHGABA -> RTN on TC loops during high sleep pressure and anesthesia. (Years 2-3)To address these questions, we propose to use technologies that we have been implementing over the last seven years. Those combine in vitro and in vivo optogenetics with mouse genetic engineering and high-density electrophysiological recording in freely-moving mice. In addition to providing important clues about the mechanism of action of GABA on the sleep-wake circuits in the brain, completion of this research project will provide us with important clues about the neural substrate, circuit dynamics and transmitters/modulators subserving integrative processing of sleep. It will further identify the long-sought GABA input to the RTN, and will eventually open new perspectives on sensory integration during sleep and states of unconsciousness.
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