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Mapping functional connectivity in barrel-related columns reveals layer- and cell type-specific microcircuits


Synaptic circuits bind together functional modules of the neocortex. We aim to clarify in a rodent model how intra- and transcolumnar microcircuits in the barrel cortex are laid out to segregate and also integrate sensory information. The primary somatosensory (barrel) cortex of rodents is the ideal model system to study these issues because there, the tactile information derived from the large facial whiskers on the snout is mapped onto so called barrel-related columns which altogether form an isomorphic map of the sensory periphery. This allows to functionally interpret the synaptic microcircuits we have been analyzing in barrel-related columns by means of whole-cell recordings, biocytin filling and mapping of intracortical functional connectivity with sublaminar specificity by computer-controlled flash-release of glutamate. We find that excitatory spiny neurons (spiny stellate, star pyramidal, and pyramidal cells) show a layer-specific connectivity pattern on top of which further cell type-specific circuits can be distinguished. The main features are: (a) strong intralaminar, intracolumnar connections are established by all types of excitatory neurons with both, excitatory and (except for layer Vb- intrinsically burst-spiking-pyramidal cells) inhibitory cells; (b) effective translaminar, intracolumnar connections become more abundant along the three main layer compartments of the canonical microcircuit, and (c) extensive transcolumnar connectivity is preferentially found in specific cell types in each of the layer compartments of a barrel-related column. These multiple sequential and parallel circuits are likely to be suitable for specific cortical processing of “what” “where” and “when” aspects of tactile information acquired by the whiskers on the snout.

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  1. Agmon A, Connors BW (1991) Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41:365–379

  2. Ahissar E, Sosnik R, Haidarliu S (2000) Transformation from temporal to rate coding in a somatosensory thalamocortical pathway. Nature 406:302–306

  3. Armstrong-James MA (1995) The nature and plasticity of sensory processing within adult rat barrel cortex. In: Jones EG, Diamond IT (eds) The barrel cortex of rodents. Plenum Press, New York, pp 333–374

  4. Armstrong-James MA, Fox K (1987) Spatiotemporal convergence and divergence in the rat S1 “barrel“ cortex. J Comp Neurol 263:265–281

  5. Armstrong-James MA, Fox K, Das-Gupta A (1992) Flow of excitation within rat barrel cortex on striking a single vibrissa. J Neurophysiol 68:1345–1358

  6. Beaulieu C (1993) Numerical data on neocortical neurons in adult rat, with special reference to the GABA population. Brain Res 609:284–292

  7. Bureau I, Saint Paul F, Svoboda K (2006) Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex. Plos Biology 4:2361–2371

  8. Callaway EM, Katz LC (1993) Photostimulation using caged glutamate reveals functional circuitry in living brain slices. Proc Natl Acad Sci USA 90:7661–7665

  9. Chagnac-Amitai Y, Connors BW (1989) Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. J Neurophysiol 62:1149–1162

  10. Chagnac-Amitai Y, Luhmann HJ, Prince DA (1990) Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features. J Comp Neurol 296:598–613

  11. de Kock CPJ, Bruno RM, Spors H, Sakmann B (2007) Layer and cell type specific suprathreshold stimulus representation in primary somatosensory cortex. J Physiol (Lond) 581:139–154

  12. Derdikman D, Yu CX, Haidarliu S, Bagdasarian K, Arieli A, Ahissar E (2006) Layer-specific touch-dependent facilitation and depression in the somatosensory cortex during active whisking. J Neurosci 26:9538–9547

  13. Diamond ME, Petersen RS, Harris JA (1999) Learning through maps: functional significance of topographic organization in primary sensory cortex. J Neurobiol 41:64–68

  14. Dodt HU, Zieglgänsberger W (1994) Infrared videomicroscopy: a new look at neuronal structure and function. Trends Neurosci 17:453–458

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

  16. Fairen A, DeFelipe J, Regidor J (1984) Nonpyramidal neurons. In: Peters A, Jones EG (eds) Cellular components of the cerebral cortex. Plenum Press, New York, pp 201–253

  17. Feldmeyer D, Egger V, Lübke J, Sakmann B (1999) Reliable synaptic connections between pairs of excitatory layer 4 neurones within a single ‘barrel’ of developing rat somatosensory cortex. J Physiol (Lond) 521:169–190

  18. Feldmeyer D, Lübke J, Sakmann B (2006) Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in the barrel cortex of juvenile rats. J Physiol (Lond) 575:583–602

  19. Feldmeyer D, Lübke J, Silver RA, Sakmann B (2002) Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. J Physiol (Lond) 538:803–822

  20. Feldmeyer D, Roth A, Sakmann B (2005) Monosynaptic connections between pairs of spiny stellate cells in layer 4 and pyramidal cells in layer 5A indicate that lemniscal and paralemniscal afferent pathways converge in the infragranular somatosensory cortex. J Neurosci 25:3423–3431

  21. Fox K (2002) Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex. Neuroscience 111:799–814

  22. Fox K, Wright N, Wallace H, Glazewski S (2003) The origin of cortical surround receptive fields studied in the barrel cortex. J Neurosci 23:8380–8391

  23. Gabbott PLA, Martin KAC, Whitteridge D (1987) Connections between pyramidal neurons in layer 5 of cat visual cortex (area 17). J Comp Neurol 259:364–381

  24. Ghazanfar AA, Nicolelis MAL (1999) Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex. Cereb Cortex 9:348–361

  25. Gilbert CD (1998) Adult cortical dynamics. Physiol Rev 78:467–485

  26. Goldman-Rakic PS (1996) Regional and cellular fractionation of working memory. Proc Natl Acad Sci USA 93:13473–13480

  27. Goldreich D, Kyriazi HT, Simons DJ (1999) Functional independence of layer IV barrels in rodent somatosensory cortex. J Neurophysiol 82:1311–1316

  28. Gottlieb JP, Keller A (1997) Intrinsic circuitry and physiological properties of pyramidal neurons in rat barrel cortex. Exp Brain Res 115:47–60

  29. Gupta A, Wang Y, Markram H (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287:273–278

  30. Hefti BJ, Smith PH (2000) Anatomy, physiology, and synaptic responses of rat layer V auditory cortical cells and effects of intracellular GABA(A) blockade. J Neurophysiol 83:2626–2638

  31. Hellwig B (2000) A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex. Biol Cybern 82:111–121

  32. Hersch SM, White EL (1981) Thalamocortical synapses involving identified neurons in mouse primary somatosensory cortex: a terminal degeneration and Golgi/EM study. J Comp Neurol 195:253–263

  33. Holmgren C, Harkany T, Svennenfors B, Zilberter Y (2003) Pyramidal cell communication within local networks in layer 2/3 of rat neocortex. J Physiol (Lond) 551:139–153

  34. Hubel DH, Wiesel TN (1962) Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J Physiol (Lond) 160:106–154

  35. Hutson KA, Masterton RB (1986) The sensory contribution of a single vibrissa’s cortical barrel. J Neurophysiol 56:1196–1223

  36. Ito M (1985) Processing of vibrissa sensory information within the rat neocortex. J Neurophysiol 54:479–490

  37. Jensen KF, Killackey HP (1987) Terminal arbors of axons projecting to the somatosensory cortex of the adult rat I. The normal morphology of specific thalamocortical afferents. J Neurosci 7:3529–3543

  38. Jones EG (1975) Varieties and distribution of non-pyramidal cells in the somatic sensory cortex of the squirrel monkey. J Comp Neurol 160:205–267

  39. Jones EG (1981) Anatomy of cerebral cortex: columnar input-output organization. In: Schmitt FO, Worden FG, Adelmann G, Dennis SG (eds) The organization of the cerebral cortex. MIT Press, Cambridge, pp 199–235

  40. Juliano SL, Jacobs SE (1995) The role of acetylcholine in barrel cortex. In: Jones EG, Diamond IT (eds) The barrel cortex of rodent. Plenum Press, New York, pp 411–434

  41. Kaas JH (1997) Topographic maps are fundamental to sensory processing. Brain Res Bull 44:107–112

  42. Kleinfeld D, Ahissar E, Diamond ME (2006) Active sensation: insights from the rodent vibrissa sensorimotor system. Curr Opin Neurobiol 16:435–444

  43. Kötter R, Schubert D, Dyhrfjeld-Johnsen J, Luhmann HJ, Staiger JF (2005) Optical release of caged glutamate for stimulation of neurons in the in vitro slice preparation. J Biomed Opt 10:011003

  44. Kötter R, Staiger JF, Zilles K, Luhmann HJ (1998) Analysing functional connectivity in brain slices by a combination of infrared video microscopy, flash photolysis of caged compounds and scanning methods. Neuroscience 86:265–277

  45. Laaris N, Carlson GC, Keller A (2000) Thalamic-evoked synaptic interactions in barrel cortex revealed by optical imaging. J Neurosci 20:1529–1537

  46. Laaris N, Keller A (2002) Functional independence of layer IV barrels. J Neurophysiol 87:1028–1034

  47. Larkman A, Mason A (1990) Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex I. Establishment of cell classes. J Neurosci 10:1407–1414

  48. Larkum ME, Zhu JJ, Sakmann B (1999) A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398:338–341

  49. Larsen DD, Callaway EM (2006) Development of layer-specific axonal arborizations in mouse primary somatosensory cortex. J Comp Neurol 494:398–414

  50. Lu SM, Lin RCS (1993) Thalamic afferents of the rat barrel cortex: a light- and electron-microscopic study using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. Somatosens Motor Res 10:1–16

  51. Lund JS (1984) Spiny stellate neurons. In: Peters A, Jones EG (eds) Cellular components of the cerebral cortex. Plenum Press, New York, pp 255–308

  52. Manns ID, Sakmann B, Brecht M (2004) Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex. J Physiol (Lond) 556:601–622

  53. Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu CZ (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5:793–807

  54. Mason A, Larkman A (1990) Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex II Electrophysiology. J Neurosci 10:1415–1428

  55. McCormick DA, Connors BW, Lighthall JW, Prince DA (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol 54:782–806

  56. Molnar Z, Cheung AFP (2006) Towards the classification of subpopulations of layer V pyramidal projection neurons. Neurosci Res 55:105–115

  57. Moore CI, Nelson SB (1998) Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J Neurophysiol 80:2882–2892

  58. Mountcastle VB (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J Neurophysiol 20:408–434

  59. Mountcastle VB (1997) The columnar organization of the neocortex. Brain 120:701–722

  60. Nicolelis MAL, Ghazanfar AA, Faggin BM, Votaw S, Oliveira LMO (1997) Reconstructing the engram - simultaneous, multisite, many single neuron recordings. Neuron 18:529–537

  61. Parra P, Gulyas AI, Miles R (1998) How many subtypes of inhibitory cells in the hippocampus? Neuron 20:983–993

  62. Peters A, Jones EG (1984) Classification of cortical neurons. In: Peters A, Jones EG (eds) Cellular components of the cerebral cortex. Plenum Press, New York, pp 107–121

  63. Petersen CCH (2003) The barrel cortex—integrating molecular, cellular and systems physiology. Pflugers Arch: Eur J Physiol 447:126–134

  64. Petersen CCH, Grinvald A, Sakmann B (2003a) Spatiotemporal dynamics of sensory responses in layer 2/3 of rat barrel cortex measured in vivo by voltage-sensitive dye imaging combined with whole-cell voltage recordings and neuron reconstructions. J Neurosci 23:1298–1309

  65. Petersen CCH, Hahn TTG, Mehta M, Grinvald A, Sakmann B (2003b) Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex. Proc Natl Acad Sci USA 100:13638–13643

  66. Petersen CCH, Sakmann B (2000) The excitatory neuronal network of rat layer 4 barrel cortex. J Neurosci 20:7579–7586

  67. Petersen CCH, Sakmann B (2001) Functionally independent columns of rat somatosensory barrel cortex revealed with voltage-sensitive dye imaging. J Neurosci 21:8435–8446

  68. Ren JQ, Aika Y, Heizmann CW, Kosaka T (1992) Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with special reference to GABAergic neurons and parvalbumin-containing neurons. Exp Brain Res 92:1–14

  69. Sakmann B (2006) Patch pipettes are more useful than initially thought: simultaneous pre- and postsynaptic recording from mammalian CNS synapses in vitro and in vivo. Pflugers Arch: Eur J Physiol 453:249–259

  70. Schubert D (2007) Observing without disturbing: how different cortical neuron classes represent tactile stimuli. J Physiol (Lond) 581:5

  71. Schubert D, Kötter R, Luhmann HJ, Staiger JF (2006) Morphology, electrophysiology and functional input connectivity of pyramidal neurons characterizes a genuine layer Va in the primary somatosensory cortex. Cereb Cortex 16:223–236

  72. Schubert D, Kötter R, Zilles K, Luhmann HJ, Staiger JF (2003) Cell type-specific circuits of cortical layer IV spiny neurons. J Neurosci 23:2961–2970

  73. Schubert D, Staiger JF, Cho N, Kötter R, Zilles K, Luhmann HJ (2001) Layer-specific intracolumnar and transcolumnar functional connectivity of layer V pyramidal cells in rat barrel cortex. J Neurosci 21:3580–3592

  74. Shepherd GMG, Svoboda K (2005) Laminar and columnar organization of ascending excitatory projections to layer 2/3 pyramidal neurons in rat barrel cortex. J Neurosci 25:5670–5679

  75. Silberberg G, Grillner S, LeBeau FE, Maex R, Markram H (2005) Synaptic pathways in neural microcircuits. Trends Neurosci 28:541–551

  76. Simons DJ (1978) Response properties of vibrissa units in rat SI somatosensory neocortex. J Neurophysiol 41:798–820

  77. Simons DJ (1995) Neuronal integration in the somatosensory whisker/barrel cortex. In: Jones EG, Diamond IT (eds) The barrel cortex of rodents. Plenum Press, New York, pp 263–289

  78. Simons DJ, Carvell GE (1989) Thalamocortical response transformation in the rat vibrissa/barrel system. J Neurophysiol 61:311–330

  79. Simons DJ, Woolsey TA (1984) Morphology of Golgi-Cox-impregnated barrel neurons in rat SmI cortex. J Comp Neurol 230:119–132

  80. Staiger JF (2006) Immediate-early gene expression in the barrel cortex. Somatosens Mot Res 23:135–146

  81. Staiger JF, Bisler S, Schleicher A, Gass P, Stehle JH, Zilles K (2000a) Exploration of a novel environment leads to the expression of inducible transcription factors in barrel-related columns. Neuroscience 99:7–16

  82. Staiger JF, Flagmeyer I, Schubert D, Zilles K, Kötter R, Luhmann HJ (2004) Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells. Cereb Cortex 14:690–701

  83. Staiger JF, Grahl E, Kötter R, Schubert D (2006) Multiple networks of pyramidal cells in layers II/III of rat barrel cortex. FENS Abstract 3, A003.23

  84. Staiger JF, Kötter R, Zilles K, Luhmann HJ (1999) Connectivity in the somatosensory cortex of the adolescent rat: an in vitro biocytin study. Anat Embryol 199:357–365

  85. Staiger JF, Kötter R, Zilles K, Luhmann HJ (2000b) Laminar characteristics of functional connectivity in rat barrel cortex revealed by stimulation with caged-glutamate. Neurosci Res 37:49–58

  86. Staiger JF, Zilles K, Freund TF (1996) Distribution of GABAergic elements postsynaptic to ventroposteromedial thalamic projections in layer IV of rat barrel cortex. Eur J Neurosci 8:2273–2285

  87. Thomson AM, Bannister AP (2003) Interlaminar connections in the neocortex. Cereb Cortex 13:5–14

  88. Thomson AM, Deuchars J (1994) Temporal and spatial properties of local circuits in neocortex. Trends Neurosci 17:119–126

  89. Tononi G, Edelman GM Sporns O (1998) Complexity and coherency: integrating information in the brain. Trends Cogn Sci 2:474–484

  90. Waite PME (2004) Trigeminal sensory system. In: Paxinos G (ed) The rat nervous system. Academic Press, San Diego, CA, pp 817–851

  91. Welker C (1971) Microelectrode delineation of fine grain somatotopic organization of SmI cerebral neocortex in albino rat. Brain Res 26:259–275

  92. Welker C, Woolsey TA (1974) Structure of layer IV in the somatosensory neocortex of the rat: description and comparison with the mouse. J Comp Neurol 158:437–454

  93. Woolsey TA, van der Loos H (1970) The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. Brain Res 17:205–242

  94. Yoshimura Y, Dantzker JLM, Callaway EM (2005) Excitatory cortical neurons form fine-scale functional networks. Nature 433:868–873

  95. Zilles K, Wree A (1995) Cortex: areal and laminar structure. In: Paxinos G (ed) The rat nervous system, Academic Press, New York, pp 649–685

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We want to cordially thank Professor Dr. Karl Zilles for his long-standing, enthusiastic support of our group, as well as Professor Dr. Heiko Luhmann for previous contributions to the success of these studies. Financial support for these studies came from the Deutsche Forschungsgemeinschaft (Sta 431/5-2, 5-4; KO 1560/6-2) and the Biologisch-Medizinische Forschungszentrum (BMFZ) of the Heinrich-Heine-University Düsseldorf. Mr. Uli Opfermann-Emmerich performed excellent histological work.

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Correspondence to Dirk Schubert.

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Schubert, D., Kötter, R. & Staiger, J.F. Mapping functional connectivity in barrel-related columns reveals layer- and cell type-specific microcircuits. Brain Struct Funct 212, 107–119 (2007).

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  • Barrel cortex
  • Columnar modules
  • Microcircuits
  • Excitatory spiny neurons
  • Caged glutamate