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Optical Imaging of Neocortical Dynamics pp 3–18Cite as

Neocortex in the Spotlight: Concepts, Questions, and Methods

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Part of the book series: Neuromethods ((NM,volume 85))

Abstract

When mammals such as mice, cats, monkeys, or humans act in the world, they continually make behaviorally relevant decisions based on perceived sensory information and memorized experiences and they constantly adapt to outside challenges through learning. These cognitive capabilities largely arise from neural processing in the outermost thin sheet of the forebrain called the neocortex. Although the mammalian neocortex has been studied extensively, the astounding complexity of both its structure and dynamics has precluded a comprehensive understanding of its function so far. Higher cortical function emerges from the interplay of myriads of diverse neocortical cells, organized across multiple hierarchical levels from local neuronal networks (“microcircuits”) to communicating brain regions (“macrocircuits”). It remains elusive how these neural circuits operate—assisted by glial networks and fuelled by the vascular system—to generate intelligent behavior and ensure adequate learning. Advances in experimental methodology are essential to further unravel cortical function and in this book we highlight the rapid recent progress in optical methods for measuring and controlling neocortical dynamics, complementing classic electrophysiological approaches. In this chapter we provide a brief overview of the functional organization of the neocortex, its tissue constituents, and current concepts of neocortical dynamics. In preparation of subsequent chapters, we summarize the manifold ways photons can be used to study neocortical function, utilizing specially designed molecular tools and various imaging technologies. We conclude with a brief future outlook. Putting neocortex literally “into the spotlight” may help uncover its intriguing mysteries.

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References

  1. Oberlaender M, de Kock CP, Bruno RM, Ramirez A, Meyer HS, Dercksen VJ, Helmstaedter M, Sakmann B (2012) Cell type-specific three-dimensional structure of thalamocortical circuits in a column of rat vibrissal cortex. Cereb Cortex 22:2375–2391

    Article  PubMed  Google Scholar 

  2. Petersen CC (2009) Barrel cortex circuits. In: Larry RS (ed) Encyclopedia of neuroscience. Academic, Oxford, pp 41–45

    Chapter  Google Scholar 

  3. Murayama M, Perez-Garci E, Nevian T, Bock T, Senn W, Larkum ME (2009) Dendritic encoding of sensory stimuli controlled by deep cortical interneurons. Nature 457:1137–1141

    Article  CAS  PubMed  Google Scholar 

  4. Douglas RJ, Martin KA (2004) Neuronal circuits of the neocortex. Annu Rev Neurosci 27:419–451

    Article  CAS  PubMed  Google Scholar 

  5. Mountcastle VB (1978) An organizing principle for cerebral function: the unit model and the distributed system. In: Edelman GM, Mountcastle VB (eds) The mindful brain. MIT, Cambridge

    Google Scholar 

  6. Bargmann CI, Marder E (2013) From the connectome to brain function. Nat Methods 10:483–490

    Article  CAS  PubMed  Google Scholar 

  7. Helmstaedter M (2013) Cellular-resolution connectomics: challenges of dense neural circuit reconstruction. Nat Methods 10:501–507

    Article  CAS  PubMed  Google Scholar 

  8. Shepherd GM, Grillner S (eds) (2010) Handbook of brain mircocircuits, 1st edn. Oxford University Press, New York

    Google Scholar 

  9. Spruston N (2008) Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 9:206–221

    Article  CAS  PubMed  Google Scholar 

  10. Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A, Buzsaki G, Cauli B, Defelipe J, Fairen A, Feldmeyer D, Fishell G, Fregnac Y, Freund TF, Gardner D, Gardner EP, Goldberg JH, Helmstaedter M, Hestrin S, Karube F, Kisvarday ZF, Lambolez B, Lewis DA, Marin O, Markram H, Munoz A, Packer A, Petersen CC, Rockland KS, Rossier J, Rudy B, Somogyi P, Staiger JF, Tamas G, Thomson AM, Toledo-Rodriguez M, Wang Y, West DC, Yuste R (2008) Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 9:557–568

    Article  CAS  PubMed  Google Scholar 

  11. Rudy B, Fishell G, Lee S, Hjerling-Leffler J (2011) Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons. Dev Neurobiol 71:45–61

    Article  PubMed Central  PubMed  Google Scholar 

  12. Silberberg G (2008) Polysynaptic subcircuits in the neocortex: spatial and temporal diversity. Curr Opin Neurobiol 18:332–337

    Article  CAS  PubMed  Google Scholar 

  13. Connors BW, Long MA (2004) Electrical synapses in the mammalian brain. Annu Rev Neurosci 27:393–418

    Article  CAS  PubMed  Google Scholar 

  14. Kettenmann H, Ransom BR (eds) (2012) Neuroglia, 3rd edn. Oxford University Press, New York

    Google Scholar 

  15. Parpura V, Heneka MT, Montana V, Oliet SH, Schousboe A, Haydon PG, Stout RF Jr, Spray DC, Reichenbach A, Pannicke T, Pekny M, Pekna M, Zorec R, Verkhratsky A (2012) Glial cells in (patho)physiology. J Neurochem 121:4–27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Parpura V, Zorec R (2010) Gliotransmission: Exocytotic release from astrocytes. Brain Res Rev 63:83–92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Tsai PS, Kaufhold JP, Blinder P, Friedman B, Drew PJ, Karten HJ, Lyden PD, Kleinfeld D (2009) Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels. J Neurosci 29:14553–14570

    Article  CAS  PubMed  Google Scholar 

  18. Hirsch S, Reichold J, Schneider M, Szekely G, Weber B (2012) Topology and hemodynamics of the cortical cerebrovascular system. J Cereb Blood Flow Metab 32:952–967

    Article  PubMed  Google Scholar 

  19. Luo L, Callaway EM, Svoboda K (2008) Genetic dissection of neural circuits. Neuron 57:634–660

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. O’Connor DH, Huber D, Svoboda K (2009) Reverse engineering the mouse brain. Nature 461:923–929

    Article  PubMed  Google Scholar 

  21. Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10:647–658

    Article  CAS  PubMed  Google Scholar 

  22. Scanziani M, Häusser M (2009) Electrophysiology in the age of light. Nature 461:930–939

    Google Scholar 

  23. Lütcke H, Margolis DJ, Helmchen F (2013) Steady or changing? Long-term monitoring of neuronal population activity. Trends Neurosci 36:375–384

    Article  PubMed  Google Scholar 

  24. Chen JL, Carta S, Soldado-Magraner J, Schneider BL, Helmchen F (2013) Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex. Nature 499:336–340

    Article  CAS  PubMed  Google Scholar 

  25. Kerlin AM, Andermann ML, Berezovskii VK, Reid RC (2010) Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex. Neuron 67:858–871

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Langer D, Helmchen F (2012) Post hoc immunostaining of GABAergic neuronal subtypes following in vivo two-photon calcium imaging in mouse neocortex. Pflügers Arch 463:339–354

    Google Scholar 

  27. Adams SR, Tsien RY (1993) Controlling cell chemistry with caged compounds. Annu Rev Physiol 55:755–784

    Article  CAS  PubMed  Google Scholar 

  28. Callaway EM, Yuste R (2002) Stimulating neurons with light. Curr Opin Neurobiol 12:587–592

    Article  CAS  PubMed  Google Scholar 

  29. Sarkisov DV, Wang SS (2006) Alignment and calibration of a focal neurotransmitter uncaging system. Nat Protoc 1:828–832

    Article  CAS  PubMed  Google Scholar 

  30. Haupts U, Tittor J, Bamberg E, Oesterhelt D (1997) General concept for ion translocation by halobacterial retinal proteins: the isomerization/switch/transfer (IST) model. Biochemistry 36:2–7

    Article  CAS  PubMed  Google Scholar 

  31. Ernst OP, Sanchez Murcia PA, Daldrop P, Tsunoda SP, Kateriya S, Hegemann P (2008) Photoactivation of channelrhodopsin. J Biol Chem 283:1637–1643

    Article  CAS  PubMed  Google Scholar 

  32. Essen LO (2002) Halorhodopsin: light-driven ion pumping made simple? Curr Opin Struct Biol 12:516–522

    Article  CAS  PubMed  Google Scholar 

  33. Hegemann P, Ehlenbeck S, Gradmann D (2005) Multiple photocycles of channelrhodopsin. Biophys J 89:3911–3918

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Schobert B, Lanyi JK (1982) Halorhodopsin is a light-driven chloride pump. J Biol Chem 257:10306–10313

    CAS  PubMed  Google Scholar 

  35. Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412

    Article  CAS  PubMed  Google Scholar 

  36. Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76

    Article  CAS  PubMed  Google Scholar 

  37. Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat Methods 2:932–940

    Article  CAS  PubMed  Google Scholar 

  38. Svoboda K, Yasuda R (2006) Principles of two-photon excitation microscopy and its applications to neuroscience. Neuron 50:823–839

    Article  CAS  PubMed  Google Scholar 

  39. Kerr JN, Denk W (2008) Imaging in vivo: watching the brain in action. Nat Rev Neurosci 9:195–205

    Article  CAS  PubMed  Google Scholar 

  40. Testa I, Urban NT, Jakobs S, Eggeling C, Willig KI, Hell SW (2012) Nanoscopy of living brain slices with low light levels. Neuron 75:992–1000

    Article  CAS  PubMed  Google Scholar 

  41. Chance B, Cohen P, Jobsis F, Schoener B (1962) Intracellular oxidation-reduction states in vivo. Science 137:499–508

    Article  CAS  PubMed  Google Scholar 

  42. Malonek D, Grinvald A (1996) Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–554

    Article  CAS  PubMed  Google Scholar 

  43. Dunn AK, Bolay H, Moskowitz MA, Boas DA (2001) Dynamic imaging of cerebral blood flow using laser speckle. J Cereb Blood Flow Metab 21:195–201

    Article  CAS  PubMed  Google Scholar 

  44. Zakharov P, Völker A, Buck A, Weber B, Scheffold F (2006) Quantitative modeling of laser speckle imaging. Opt Lett 31:3465–3467

    Article  PubMed  Google Scholar 

  45. Lothman E, Lamanna J, Cordingley G, Rosenthal M, Somjen G (1975) Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res 88:15–36

    Article  CAS  PubMed  Google Scholar 

  46. Mayevsky A, Chance B (1975) Metabolic responses of the awake cerebral cortex to anoxia hypoxia spreading depression and epileptiform activity. Brain Res 98:149–165

    Article  CAS  PubMed  Google Scholar 

  47. Shibuki K, Hishida R, Murakami H, Kudoh M, Kawaguchi T, Watanabe M, Watanabe S, Kouuchi T, Tanaka R (2003) Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J Physiol 549:919–927

    Article  CAS  PubMed  Google Scholar 

  48. Ferezou I, Haiss F, Gentet LJ, Aronoff R, Weber B, Petersen CC (2007) Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice. Neuron 56:907–923

    Article  CAS  PubMed  Google Scholar 

  49. Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5:874–885

    Article  CAS  PubMed  Google Scholar 

  50. Berger T, Borgdorff A, Crochet S, Neubauer FB, Lefort S, Fauvet B, Ferezou I, Carleton A, Luscher HR, Petersen CC (2007) Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex. J Neurophysiol 97:3751–3762

    Article  CAS  PubMed  Google Scholar 

  51. Minderer M, Liu W, Sumanovski LT, Kügler S, Helmchen F, Margolis DJ (2012) Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator. J Physiol 590:99–107

    Google Scholar 

  52. Adelsberger H, Garaschuk O, Konnerth A (2005) Cortical calcium waves in resting newborn mice. Nat Neurosci 8:988–990

    Article  CAS  PubMed  Google Scholar 

  53. Schulz K, Sydekum E, Krueppel R, Engelbrecht CJ, Schlegel F, Schroter A, Rudin M, Helmchen F (2012) Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex. Nat Methods 9:597–602

    Article  CAS  PubMed  Google Scholar 

  54. Stroh A, Adelsberger H, Groh A, Ruhlmann C, Fischer S, Schierloh A, Deisseroth K, Konnerth A (2013) Making waves: initiation and propagation of corticothalamic Ca2+ waves in vivo. Neuron 77:1136–1150

    Article  CAS  PubMed  Google Scholar 

  55. Devor A, Boas D (2012) Neurovascular imaging. Front Neuroenergetics 4:1

    Article  PubMed Central  PubMed  Google Scholar 

  56. Petersen CC, Crochet S (2013) Synaptic computation and sensory processing in neocortical layer 2/3. Neuron 78:28–48

    Article  CAS  PubMed  Google Scholar 

  57. Osten P, Margrie TW (2013) Mapping brain circuitry with a light microscope. Nat Methods 10:515–523

    Article  CAS  PubMed  Google Scholar 

  58. Denk W, Briggman KL, Helmstaedter M (2012) Structural neurobiology: missing link to a mechanistic understanding of neural computation. Nat Rev Neurosci 13:351–358

    CAS  PubMed  Google Scholar 

  59. Briggman KL, Helmstaedter M, Denk W (2011) Wiring specificity in the direction-selectivity circuit of the retina. Nature 471:183–188

    Article  CAS  PubMed  Google Scholar 

  60. Bock DD, Lee WC, Kerlin AM, Andermann ML, Hood G, Wetzel AW, Yurgenson S, Soucy ER, Kim HS, Reid RC (2011) Network anatomy and in vivo physiology of visual cortical neurons. Nature 471:177–182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Ko H, Hofer SB, Pichler B, Buchanan KA, Sjostrom PJ, Mrsic-Flogel TD (2011) Functional specificity of local synaptic connections in neocortical networks. Nature 473:87–91

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Lichtman JW, Denk W (2011) The big and the small: challenges of imaging the brain’s circuits. Science 334:618–623

    Article  CAS  PubMed  Google Scholar 

  63. Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R (2012) The brain activity map project and the challenge of functional connectomics. Neuron 74:970–974

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Devor A, Bandettini PA, Boas DA, Bower JM, Buxton RB, Cohen LB, Dale AM, Einevoll GT, Fox PT, Franceschini MA, Friston KJ, Fujimoto JG, Geyer MA, Greenberg JH, Halgren E, Hämäläinen MS, Helmchen F, Hyman BT, Jasanoff A, Jernigan TL, Judd LL, Kim SG, Kleinfeld D, Kopell NJ, Kutas M, Kwong KK, Larkum ME, Lo EH, Magistretti PJ, Mandeville JB, Masliah E, Mitra PP, Mobley WC, Moskowitz MA, Nimmerjahn A, Reynolds JH, Rosen BR, Salzberg BM, Schaffer CB, Silva GA, So PTC, Spitzer NC, Tootell RB, Van Essen DC, Vanduffel W, Vinogradov SA, Wald LL, Wang LV, Weber B, Yodh AG (2013). The Challenge of Connecting the Dots in the B.R.A.I.N. Neuron 80:270–274

    Google Scholar 

  65. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640

    Article  CAS  PubMed  Google Scholar 

  66. Clarke LE, Barres BA (2013) Emerging roles of astrocytes in neural circuit development. Nat Rev Neurosci 14:311–321

    Article  CAS  PubMed  Google Scholar 

  67. Garaschuk O (2013) Imaging microcircuit function in healthy and diseased brain. Exp Neurol 242:41–49

    Article  PubMed  Google Scholar 

  68. Tye KM, Deisseroth K (2012) Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci 13:251–266

    Article  CAS  PubMed  Google Scholar 

  69. Aramuni G, Griesbeck O (2013) Chronic calcium imaging in neuronal development and disease. Exp Neurol 242:50–56

    Article  CAS  PubMed  Google Scholar 

  70. Aguzzi A, Barres BA, Bennett ML (2013) Microglia: scapegoat, saboteur, or something else? Science 339:156–161

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Brain Research Institute, University of Zurich, Zurich, Switzerland

    Fritjof Helmchen

  2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

    Bruno Weber

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  1. Fritjof Helmchen
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  2. Bruno Weber
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Editors and Affiliations

  1. University of Zurich, Switzerland

    Bruno Weber

  2. University of Zurich, Switzerland

    Fritjof Helmchen

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Helmchen, F., Weber, B. (2014). Neocortex in the Spotlight: Concepts, Questions, and Methods. In: Weber, B., Helmchen, F. (eds) Optical Imaging of Neocortical Dynamics. Neuromethods, vol 85. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-785-3_1

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  • DOI: https://doi.org/10.1007/978-1-62703-785-3_1

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-784-6

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