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Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs

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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.

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Acknowledgments

The authors thank Célya Gruson-Daniel, Anastassios Karagiannis, Uwe Maskos, Stéphanie Pons, Martine Soudan and the IBPS Cell Imaging Facility for their valuable help. This work was supported by Centre National de la Recherche Scientifique, Université Pierre et Marie Curie-P6 and by grants from Ecole des Neurosciences de Paris (“Network for Viral Transfer”), Fondation pour la Recherche sur le Cerveau/Rotary Club de France and Agence Nationale de la Recherche (“IHU Institut de Neurosciences Translationelles de Paris”).

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  1. UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France

    Y Audrey Hay, Sofija Andjelic, Sammy Badr & Bertrand Lambolez

  2. UMR 8246, Centre National de la Recherche Scientifique (CNRS), Paris, France

    Y Audrey Hay, Sofija Andjelic, Sammy Badr & Bertrand Lambolez

  3. UMR-S 1130, Institut national de la Santé et de la Recherche Médicale (INSERM), Paris, France

    Y Audrey Hay, Sofija Andjelic, Sammy Badr & Bertrand Lambolez

  4. UMR 8246, Neuroscience Paris Seine, Université Pierre et Marie Curie, 9 quai St Bernard case 16, 75005, Paris, France

    Bertrand Lambolez

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  1. Y Audrey Hay
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Correspondence to Bertrand Lambolez.

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S. Andjelic and S. Badr are equal contributors.

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Hay, Y.A., Andjelic, S., Badr, S. et al. Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs. Brain Struct Funct 220, 3497–3512 (2015). https://doi.org/10.1007/s00429-014-0869-7

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  • DOI: https://doi.org/10.1007/s00429-014-0869-7

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