Brain Structure and Function

, Volume 220, Issue 6, pp 3497–3512 | Cite as

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

  • Y Audrey Hay
  • Sofija Andjelic
  • Sammy Badr
  • Bertrand Lambolez
Original Article
First Online:
Received:
Accepted:

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.

Keywords

Cerebral cortex Layer 6  Hypocretin  Acetylcholine  Midline thalamus 
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Notes

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”).

References

  1. Andjelic S, Gallopin T, Cauli B, Hill EL, Roux L, Badr S, Hu E, Tamas G, Lambolez B (2009) Glutamatergic nonpyramidal neurons from neocortical layer VI and their comparison with pyramidal and spiny stellate neurons. J Neurophysiol 101:641–654PubMedCentralCrossRefPubMedGoogle Scholar
  2. Arimatsu Y, Ishida M, Kaneko T, Ichinose S, Omori A (2003) Organization and development of corticocortical associative neurons expressing the orphan nuclear receptor Nurr1. J Comp Neurol 466:180–196CrossRefPubMedGoogle Scholar
  3. Arroyo S, Bennett C, Aziz D, Brown SP, Hestrin S (2012) Prolonged disynaptic inhibition in the cortex mediated by slow, non-alpha7 nicotinic excitation of a specific subset of cortical interneurons. J Neurosci 32:3859–3864PubMedCentralCrossRefPubMedGoogle Scholar
  4. Bailey CDC, De Biasi M, Fletcher PJ, Lambe EK (2010) The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy. J Neurosci 30:9241–9252PubMedCentralCrossRefPubMedGoogle Scholar
  5. Bayer L, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M, Serafin M (2002) Selective action of orexin (hypocretin) on nonspecific thalamocortical projection neurons. J Neurosci 22:7835–7839PubMedGoogle Scholar
  6. Bayer L, Serafin M, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M (2004) Exclusive postsynaptic action of hypocretin-orexin on sublayer 6b cortical neurons. J Neurosci 24:6760–6764CrossRefPubMedGoogle Scholar
  7. Bennett C, Arroyo S, Berns D, Hestrin S (2012) Mechanisms generating dual-component nicotinic EPSCs in cortical interneurons. J Neurosci 32:17287–17296PubMedCentralCrossRefPubMedGoogle Scholar
  8. Berendse HW, Groenewegen HJ (1991) Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat. Neuroscience 42:73–102CrossRefPubMedGoogle Scholar
  9. Beuckmann CT, Yanagisawa M (2002) Orexins: from neuropeptides to energy homeostasis and sleep/wake regulation. J Mol Med 80:329–342CrossRefPubMedGoogle Scholar
  10. Bochet P, Audinat E, Lambolez B, Crepel F, Rossier J, Iino M, Tsuzuki K, Ozawa S (1994) Subunit composition at the single-cell level explains functional properties of a glutamate-gated channel. Neuron 12:383–388CrossRefPubMedGoogle Scholar
  11. Cauli B, Lambolez B (2010) Gene analysis of single cells. In: Bontoux N, Potier MC (eds) Unravelling single cell genomics, RSC nanoscience and nanotechnology No 15, The Royal Society of Chemistry, pp 81–92Google Scholar
  12. Cauli B, Audinat E, Lambolez B, Angulo MC, Ropert N, Tsuzuki K, Hestrin S, Rossier J (1997) Molecular and physiological diversity of cortical nonpyramidal cells. J Neurosci 17:3894–3906PubMedGoogle Scholar
  13. Chen CC, Abrams S, Pinhas A, Brumberg JC (2009) Morphological heterogeneity of layer VI neurons in mouse barrel cortex. J Comp Neurol 512:726–746PubMedCentralCrossRefPubMedGoogle Scholar
  14. Cholvin T, Loureiro M, Cassel R, Cosquer B, Geiger K, De Sa Nogueira D, Raingard H, Robelin L, Kelche C, Pereira de Vasconcelos A, Cassel JC (2013) The ventral midline thalamus contributes to strategy shifting in a memory task requiring both prefrontal cortical and hippocampal functions. J Neurosci 33:8772–8783CrossRefPubMedGoogle Scholar
  15. Christophe E, Roebuck A, Staiger JF, Lavery DJ, Charpak S, Audinat E (2002) Two types of nicotinic receptors mediate an excitation of neocortical layer I interneurons. J Neurophysiol 88:1318–1327PubMedGoogle Scholar
  16. Clancy B, Cauller LJ (1999) Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex. J Comp Neurol 407:275–286CrossRefPubMedGoogle Scholar
  17. Code RA, Winer JA (1985) Commissural neurons in layer III of cat primary auditory cortex (AI): pyramidal and non-pyramidal cell input. J Comp Neurol 242:485–510CrossRefPubMedGoogle Scholar
  18. Crunelli V, Kelly JS, Leresche N, Pirchio M (1987) On the excitatory post-synaptic potential evoked by stimulation of the optic tract in the rat lateral geniculate nucleus. J Physiol 384:603–618PubMedCentralCrossRefPubMedGoogle Scholar
  19. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327PubMedCentralCrossRefPubMedGoogle Scholar
  20. Eckenstein FP, Baughman RW, Quinn J (1988) An anatomical study of cholinergic innervation in rat cerebral cortex. Neuroscience 25:274–457CrossRefGoogle Scholar
  21. Ferezou I, Hill EL, Cauli B, Gibelin N, Kaneko T, Rossier J, Lambolez B (2007) Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons. Cereb Cortex 17:1948–1957CrossRefPubMedGoogle Scholar
  22. Gallopin T, Geoffroy H, Rossier J, Lambolez B (2006) Cortical sources of CRF, NKB, and CCK and their effects on pyramidal cells in the neocortex. Cereb Cortex 16:1440–1452CrossRefPubMedGoogle Scholar
  23. Gulledge AT, Stuart GJ (2005) Cholinergic inhibition of neocortical pyramidal neurons. J Neurosci 25:10308–10320CrossRefPubMedGoogle Scholar
  24. Hembrook JR, Mair RG (2011) Lesions of reuniens and rhomboid thalamic nuclei impair radial maze win-shift performance. Hippocampus 21:815–826PubMedCentralPubMedGoogle Scholar
  25. Herkenham M (1980) Laminar organization of thalamic projections to the rat neocortex. Science 207:532–535CrossRefPubMedGoogle Scholar
  26. Hirsch JA, Gallagher CA, Alonso JM, Martinez LM (1998) Ascending projections of simple and complex cells in layer 6 of the cat striate cortex. J Neurosci 18:8086–8094PubMedGoogle Scholar
  27. Hu E, Demmou L, Cauli B, Gallopin T, Geoffroy H, Harris-Warrick RM, Paupardin-Tritsch D, Lambolez B, Vincent P, Hepp R (2011) VIP, CRF, and PACAP act at distinct receptors to elicit different cAMP/PKA dynamics in the neocortex. Cereb Cortex 21:708–718PubMedCentralCrossRefPubMedGoogle Scholar
  28. Jahnsen H, Llinás R (1984) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol 349:205–226PubMedCentralCrossRefPubMedGoogle Scholar
  29. Jasper H, Ajmone-Marsan C, Hanbery J (1953) Pathways and functional properties of the nonspecific thalamo-cortical projection system. Trans Am Neurol Assoc 3:9–11PubMedGoogle Scholar
  30. Jones E (2007) Principles of thalamic organization. In: Jones E (ed) The Thalamus, 2nd edn. Cambridge University Press, pp 87–170Google Scholar
  31. Karagiannis A, Gallopin T, David C, Battaglia D, Geoffroy H, Rossier J, Hillman EM, Staiger JF, Cauli B (2009) Classification of NPY-expressing neocortical interneurons. J Neurosci 29:3642–3659PubMedCentralCrossRefPubMedGoogle Scholar
  32. Kassam SM, Herman PM, Goodfellow NM, Alves NC, Lambe EK (2008) Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors. J Neurosci 28:8756–8764PubMedCentralCrossRefPubMedGoogle Scholar
  33. Kuryatov A, Onksen J, Lindstrom J (2008) Roles of accessory subunits in alpha4 beta2* nicotinic receptors. Mol Pharmacol 74:132–143CrossRefPubMedGoogle Scholar
  34. Lambe EK, Aghajanian GK (2003) Hypocretin (orexin) induces calcium transients in single spines postsynaptic to identified thalamocortical boutons in prefrontal slice. Neuron 40:139–150CrossRefPubMedGoogle Scholar
  35. Lambolez B, Audinat E, Bochet P, Crepel F, Rossier J (1992) AMPA receptor subunits expressed by single Purkinje cells. Neuron 9:247–258CrossRefPubMedGoogle Scholar
  36. Loureiro M, Cholvin T, Lopez J, Merienne N, Latreche A, Cosquer B, Geiger K, Kelche C, Cassel JC, Pereira de Vasconcelos A (2012) The ventral midline thalamus (reuniens and rhomboid nuclei) contributes to the persistence of spatial memory in rats. J Neurosci 32:9947–9959CrossRefPubMedGoogle Scholar
  37. Marubio LM, Changeux J (2000) Nicotinic acetylcholine receptor knockout mice as animal models for studying receptor function. Eur J Pharmacol 393:113–121CrossRefPubMedGoogle Scholar
  38. Marx M, Feldmeyer D (2013) Morphology and physiology of excitatory neurons in layer 6b of the somatosensory rat barrel cortex. Cereb Cortex 23:2803–2817PubMedCentralCrossRefPubMedGoogle Scholar
  39. Maskos U, Molles BE, Pons S, Besson M, Guiard BP, Guilloux JP, Evrard A, Cazala P, Cormier A, Mameli-Engvall M, Dufour N, Cloëz-Tayarani I, Bemelmans AP, Mallet J, Gardier AM, David V, Faure P, Granon S, Changeux JP (2005) Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature 436:103–107CrossRefPubMedGoogle Scholar
  40. McCormick DA, Bal T (1997) Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185–215CrossRefPubMedGoogle Scholar
  41. Mercer A, West DC, Morris OT, Kirchhecker S, Kerkhoff JE, Thomson AM (2005) Excitatory connections made by presynaptic cortico-cortical pyramidal cells in layer 6 of the neocortex. Cereb Cortex 15:1485–1496CrossRefPubMedGoogle Scholar
  42. Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the eeg. Electroencephalogr Clin Neurophysiol 1:455–473CrossRefPubMedGoogle Scholar
  43. Osten P, Dittgen T, Licznerski P (2006) Lentivirus-based genetic manipulations in neurons In Vivo. In: Kittler JT, Moss SJ (eds) The Dynamic synapse: molecular methods in Ionotropic Receptor Biology chapter 13. CRC Press, Boca RatonGoogle Scholar
  44. Perrenoud Q, Rossier J, Geoffroy H, Vitalis T, Gallopin T (2013) Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex. Cereb Cortex 23:423–441CrossRefPubMedGoogle Scholar
  45. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015PubMedGoogle Scholar
  46. Poorthuis RB, Bloem B, Verhoog MB, Mansvelder HD (2013) Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine. J Neurosci 33:4843–4853CrossRefPubMedGoogle Scholar
  47. Porter JT, Cauli B, Tsuzuki K, Lambolez B, Rossier J, Audinat E (1999) Selective excitation of subtypes of neocortical interneurons by nicotinic receptors. J Neurosci 19:5228–5235PubMedGoogle Scholar
  48. Prieto JJ, Winer JA (1999) Layer VI in cat primary auditory cortex: golgi study and sublaminar origins of projection neurons. J Comp Neurol 404:332–358CrossRefPubMedGoogle Scholar
  49. Ramirez-Latorre J, Yu CR, Qu X, Perin F, Karlin A, Role L (1996) Functional contributions of alpha5 subunit to neuronal acetylcholine receptor channels. Nature 380:347–351CrossRefPubMedGoogle Scholar
  50. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585CrossRefPubMedGoogle Scholar
  51. Stuart GJ, Dodt HU, Sakmann B (1993) Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch 423:511–518CrossRefPubMedGoogle Scholar
  52. Tömböl T (1984) Layer VI Cells. Cerebral Cortex. Plenum, New York and London, pp 479–520Google Scholar
  53. Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438:71–75CrossRefPubMedGoogle Scholar
  54. Tsuzuki K, Lambolez B, Rossier J, Ozawa S (2001) Absolute quantification of AMPA receptor subunit mRNAs in single hippocampal neurons. J Neurochem 77:1650–1659CrossRefPubMedGoogle Scholar
  55. Usrey WM, Fitzpatrick D (1996) Specificity in the axonal connections of layer VI neurons in tree shrew striate cortex: evidence for distinct granular and supragranular systems. J Neurosci 16:1203–1218PubMedGoogle Scholar
  56. Valverde F, Facal-Valverde MV, Santacana M, Heredia M (1989) Development and differentiation of early generated cells of sublayer VIb in the somatosensory cortex of the rat: a correlated Golgi and autoradiographic study. J Comp Neurol. 290:118–140CrossRefPubMedGoogle Scholar
  57. van Brederode JF, Snyder GL (1992) A comparison of the electrophysiological properties of morphologically identified cells in layers 5B and 6 of the rat neocortex. Neuroscience 50:315–337CrossRefPubMedGoogle Scholar
  58. Van der Werf YD, Witter MP, Groenewegen HJ (2002) The intralaminar and midline nuclei of the thalamus. anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Brain Res Rev 39:107–140CrossRefPubMedGoogle Scholar
  59. Vertes RP (2006) Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142:1–20CrossRefPubMedGoogle Scholar
  60. Vertes RP, Hoover WB, Do Valle AC, Sherman A, Rodriguez JJ (2006) Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat. J Comp Neurol 499:768–796CrossRefPubMedGoogle Scholar
  61. Winzer-Serhan UH, Leslie FM (2005) Expression of alpha5 nicotinic acetylcholine receptor subunit mRNA during hippocampal and cortical development. J Comp Neurol 481:19–30CrossRefPubMedGoogle Scholar
  62. Xiang Z, Huguenard JR, Prince DA (1998) Cholinergic switching within neocortical inhibitory networks. Science 281:985–988CrossRefPubMedGoogle Scholar
  63. Zhang ZW, Deschenes M (1997) Intracortical axonal projections of lamina VI cells of the primary somatosensory cortex in the rat: a single-cell labeling study. J Neurosci 17:6365–6379PubMedGoogle Scholar
  64. Zhang ZW, Deschenes M (1998) Projections to layer VI of the posteromedial barrel field in the rat: a reappraisal of the role of corticothalamic pathways. Cereb Cortex 8:428–436CrossRefPubMedGoogle Scholar
  65. Zhang F, Aravanis AM, Adamantidis A, de Lecea L, Deisseroth K (2007) Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci 8:577–581CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Y Audrey Hay
    • 1
    • 2
    • 3
  • Sofija Andjelic
    • 1
    • 2
    • 3
  • Sammy Badr
    • 1
    • 2
    • 3
  • Bertrand Lambolez
    • 1
    • 2
    • 3
    • 4
  1. 1.UM CR 18, Neuroscience Paris SeineSorbonne Universités, UPMC Univ Paris 06ParisFrance
  2. 2.UMR 8246Centre National de la Recherche Scientifique (CNRS)ParisFrance
  3. 3.UMR-S 1130Institut national de la Santé et de la Recherche Médicale (INSERM)ParisFrance
  4. 4.UMR 8246, Neuroscience Paris SeineUniversité Pierre et Marie CurieParisFrance

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