Wake; Sleep; Optogenetics; Neural circuits; Thalamus; Hypothalamus
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.
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.
Gent Thomas C, Bassetti Claudio LA, Adamantidis Antoine R (2018), Sleep-wake control and the thalamus, in Current Opinion in Neurobiology
, 52, 188-197.
Ferreira Jozelia Gomes Pacheco, Bittencourt Jackson Cioni, Adamantidis Antoine (2017), Melanin-concentrating hormone and sleep, in Current Opinion in Neurobiology
, 44, 152-158.
Boyce Richard, Williams Sylvain, Adamantidis Antoine (2017), REM sleep and memory, in Current Opinion in Neurobiology
, 44, 167-177.
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.
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.
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.
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.
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.
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.