caa a22 4500 606201750 CHVBK 20210128100950.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00429-014-0869-7 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0869-7 Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs [Elektronische Daten] [Y Hay, Sofija Andjelic, Sammy Badr, Bertrand Lambolez] 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. Springer-Verlag Berlin Heidelberg, 2014 Cerebral cortex nationallicence Layer 6 nationallicence Hypocretin nationallicence Acetylcholine nationallicence Midline thalamus nationallicence Hay Y. UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut Andjelic Sofija UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut Badr Sammy UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut Lambolez Bertrand UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3497-3512 1863-2653 220:6<3497 2015 220 429 https://doi.org/10.1007/s00429-014-0869-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0869-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hay Y. UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut NATIONALLICENCE 700 1- Andjelic Sofija UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut NATIONALLICENCE 700 1- Badr Sammy UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut NATIONALLICENCE 700 1- Lambolez Bertrand UM CR 18, Neuroscience Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, 75005, Paris, France aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3497-3512 1863-2653 220:6<3497 2015 220 429