title: Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs.
abstract: Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices. We found that the majority of layer VIb neurons were excited by nicotinic agonists and orexin through the activation of nicotinic receptors containing α4-α5-β2 subunits and OX2 receptor, respectively. Specific effects of orexin on layer VIb neurons were potentiated by low nicotine concentrations and we used this paradigm to explore their intracortical projections. Co-application of nicotine and orexin increased the frequency of excitatory post-synaptic currents in the ipsilateral cortex, with maximal effect in infragranular layers and minimal effect in layer IV, as well as in the contralateral cortex. The ability of layer VIb to relay thalamocortical inputs was tested using photostimulation of channelrhodopsin-expressing fibers from the orexin-sensitive rhomboid nucleus in the parietal cortex. Photostimulation induced robust excitatory currents in layer VIa neurons that were not pre-synaptically modulated by orexin, but exhibited a delayed, orexin-dependent, component. Activation of layer VIb by orexin enhanced the reliability and spike-timing precision of layer VIa responses to rhomboid inputs. These results indicate that layer VIb acts as an orexin-gated excitatory feedforward loop that potentiates thalamocortical arousal.
authors.affiliation: UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France. audrey.hay@normalesup.org.|UMR 8246, Centre National de la Recherche Scientifique (CNRS), Paris, France. audrey.hay@normalesup.org.|UMR-S 1130, Institut national de la Santé et de la Recherche Médicale (INSERM), Paris, France. audrey.hay@normalesup.org.
authors.forename: Y Audrey
authors.initials: YA
authors.lastname: Hay
authors.affiliation: UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France.|UMR 8246, Centre National de la Recherche Scientifique (CNRS), Paris, France.|UMR-S 1130, Institut national de la Santé et de la Recherche Médicale (INSERM), Paris, France.
authors.forename: Sofija
authors.initials: S
authors.lastname: Andjelic
authors.affiliation: UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France.|UMR 8246, Centre National de la Recherche Scientifique (CNRS), Paris, France.|UMR-S 1130, Institut national de la Santé et de la Recherche Médicale (INSERM), Paris, France.
authors.forename: Sammy
authors.initials: S
authors.lastname: Badr
authors.affiliation: UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France. bertrand.lambolez@snv.jussieu.fr.|UMR 8246, Centre National de la Recherche Scientifique (CNRS), Paris, France. bertrand.lambolez@snv.jussieu.fr.|UMR-S 1130, Institut national de la Santé et de la Recherche Médicale (INSERM), Paris, France. bertrand.lambolez@snv.jussieu.fr.|UMR 8246, Neuroscience Paris Seine, Université Pierre et Marie Curie, 9 quai St Bernard case 16, 75005, Paris, France. bertrand.lambolez@snv.jussieu.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lambolez
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D020644:Midline Thalamic Nuclei / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D062308:Optogenetics; D000068797:Orexins / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D055366:Synaptic Potentials / Q000187:drug effects
chemical_list: D018722:Nicotinic Agonists; D000068797:Orexins; D004246:Dimethylphenylpiperazinium Iodide
keywords: Acetylcholine; Cerebral cortex; Hypocretin; Layer 6; Midline thalamus