title: Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.
abstract: During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity.
authors.affiliation: Department of Neurology, Inselspital University Hospital, University of Bern, Bern, Switzerland.|Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.|Department of Preclinical Research (DKF), University of Bern, Bern, Switzerland.
authors.forename: Carolina Gutierrez
authors.initials: CG
authors.lastname: Herrera
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP)/NeuroCure Cluster of Excellence, Berlin, Germany.
authors.forename: Marta Carus
authors.initials: MC
authors.lastname: Cadavieco
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jego
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP)/NeuroCure Cluster of Excellence, Berlin, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Ponomarenko
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP)/NeuroCure Cluster of Excellence, Berlin, Germany.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Korotkova
authors.affiliation: Department of Neurology, Inselspital University Hospital, University of Bern, Bern, Switzerland.|Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.|Department of Preclinical Research (DKF), University of Bern, Bern, Switzerland.
authors.forename: Antoine
authors.identifier: http://orcid.org/0000-0003-2531-5175
authors.initials: A
authors.lastname: Adamantidis
mesh_terms: D000758:Anesthesia; D000818:Animals; D001143:Arousal / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D003243:Consciousness / Q000502:physiology*; D003700:Delta Rhythm; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology; D062308:Optogenetics; D012890:Sleep / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology; D013788:Thalamus / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid