Abstract
The neocortex of higher mammals consists of six layers and three major populations of neurons, the majority of which are excitatory pyramidal cells in layers 2/3, 5 and 6, so-called spiny stellate and star pyramidal neurons in layer 4 and a very heterogeneous population of GABAergic interneurons found throughout all cortical layers. These neurons form individual, highly specific microcircuits with each other thereby forming networks like the cortical column. This chapter will summarize and discuss the axonal arborization of principal excitatory neurons and it’s implication for neocortical connectivity. It was long thought that pyramidal cells represent a rather stereotyped class of neurons both with respect to their dendritic configuration and their axonal arborization. There is, however, growing evidence that pyramidal cells show profound structural and functional differences, not only between cortical layers but also within a given layer. Principal neurons except spiny stellate neurons and star pyramidal cells in layer 4 generally have two axonal domains: a vertically oriented domain that projects throughout the cortical column into the white matter and from there either to the contralateral hemisphere or to various subcortical brain regions. The second domain forms a discontinuous system of long-range horizontal projections either within a given cortical or between cortical areas within a given sensory or even between different sensory systems. In summary, principal excitatory neurons in the neocortex vary substantially in their axonal projection patterns and the cellular as well as subcellular input and target specificity of their axons thereby contributing to the enormous computational capacity of the neocortex.
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References
Anderson JC, Douglas RJ, Martin KA, Nelson JC (1994) Synaptic output of physiologically identified spiny stellate neurons in cat visual cortex. J Comp Neurol 341:16–24
Arimatsu Y, Ishida M (2002) Distinct neuronal populations specified to form corticocortical and corticothalamic projections from layer VI of developing cerebral cortex. Neuroscience 114:1033–1045
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
Beierlein M, Gibson JR, Connors BW (2003) Two dynamically distinct inhibitory networks in layer 4 of the neocortex. J Neurophysiol 90:2987–3000
Bender KJ, Rangel J, Feldman DE (2003) Development of columnar topography in the excitatory layer 4 to layer 2/3 projection in rat barrel cortex. J Neurosci 23:8759–8770
Betz W (1874) Anatomischer Nachweis zweier Gehirncentra. Centralblatt für die medizinischen Wissenschaften 12:578–580, 595–599
Braitenberg V, Schüz A (1991) Anatomy of the cortex. Statistics and geometry (Studies of Brain Function), Vol. 18. Springer, Heidelberg, Berlin, New York
Bruno RM, Hahn TT, Wallace DJ, de Kock CP, Sakmann B (2009) Sensory experience alters specific branches of individual corticocortical axons during development. J Neurosci 29:3172–3181
Bueno-Lopez JL, Reblet C, Lopez-Medina A, Gomez-Urquijo SM, Grandes P, Gondra J, Hennequet L (1991) Targets and laminar distribution of projection neurons with ‘inverted’ morphology in rabbit cortex. Eur J Neurosci 3:415–430
Bureau I, von Saint Paul F, Svoboda K (2006) Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex. PLoS Biol 4:e382
Cauli B, Porter JT, Tsuzuki K, Lambolez B, Rossier J, Quenet B, Audinat E (2000) Classification of fusiform neocortical interneurons based on unsupervised clustering. Proc Natl Acad Sci USA 97:6144–6149
Chen CC, Abrams S, Pinhas A, Brumberg JC (2009) Morphological heterogeneity of layer VI neurons in mouse barrel cortex. J Comp Neurol 512:726–746
Clancy B, Cauller LJ (1999) Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex. J Comp Neurol 407:275–286
DeFelipe J (2005) Reflections on the structure of the cortical minicolumn. In: Casanova F (ed) Neocortical modularity and the cell minicolumn. Nova Science Publishers, New York, pp 57–92
DeFelipe J, Farinas I (1992) The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog Neurobiol 39:563–607
Egger V, Nevian T, Bruno RM (2008) Subcolumnar dendritic and axonal organization of spiny stellate and star pyramid neurons within a barrel in rat somatosensory Cortex. Cereb Cortex 18:876–889
Escobar MI, Pimienta H, Caviness VS Jr, Jacobson M, Crandall JE, Kosik KS (1986) Architecture of apical dendrites in the murine neocortex: dual apical dendritic systems. Neuroscience 17:975–989
Feldman ML (1984) Morphology of the neocortical pyramidal neurons. In: Peters A, Jones EG (eds) Cerebral cortex volume 1 cellular components of the cerebral cortex. Plenum Press, New York, pp 123–200
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-London 521(Pt 1):169–190
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-London 575:583–602
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-London 538:803–822
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
Fitzpatrick D (1996) The functional organization of local circuits in visual cortex: insights from the study of tree shrew striate cortex. Cereb Cortex 6:329–341
Fleischhauer K, Petsche H, Wittkowski W (1972) Vertical bundles of dendrites in the neocortex. Z Anat Entwicklungsgesch 136:213–223
Frick A, Feldmeyer D, Helmstaedter M, Sakmann B (2008) Monosynaptic connections between pairs of L5A pyramidal neurons in columns of juvenile rat somatosensory cortex. Cereb Cortex 18:397–406
Frotscher M (1998) Cajal-Retzius cells, reelin, and the formation of layers. Curr Opin Neurobiol 8:570–575
Gabbott PL, Martin KA, Whitteridge D (1987) Connections between pyramidal neurons in layer 5 of cat visual cortex (area 17) J Comp Neurol 259:364–381
Gilbert CD, Wiesel TN (1979) Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex. Nature 280:120–125
Gilbert CD, Wiesel TN (1983) Clustered intrinsic connections in cat visual cortex. J Neurosci 3:1116–1133
Gottlieb JP, Keller A (1997) Intrinsic circuitry and physiological properties of pyramidal neurons in rat barrel cortex. Exp Brain Res 115:47–60
Gupta A, Wang Y, Markram H (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287:273–278
Harris RM, Woolsey TA (1981) Dendritic plasticity in mouse barrel cortex following postnatal vibrissa follicle damage. J Comp Neurol 196:357–376
Harris RM, Woolsey TA (1983) Computer-assisted analyses of barrel neuron axons and their putative synaptic contacts. J Comp Neurol 220:63–79
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
Hellwig B, Schuz A, Aertsen A (1994) Synapses on axon collaterals of pyramidal cells are spaced at random intervals: a Golgi study in the mouse cerebral cortex. Biol Cybern 71:1–12
Helmstaedter M, Sakmann B, Feldmeyer D (2009a) L2/3 interneuron groups defined by multiparameter analysis of axonal projection, dendritic geometry, and electrical excitability. Cereb Cortex 19:951–962
Helmstaedter M, Sakmann B, Feldmeyer D (2009b) Neuronal correlates of local, lateral, and translaminar inhibition with reference to cortical columns. Cereb Cortex 19:926–937
Helmstaedter M, Sakmann B, Feldmeyer D (2009c) The relation between dendritic geometry, electrical excitability, and axonal projections of L2/3 Interneurons in rat barrel cortex. Cereb Cortex 19:938–950
Helmstaedter M, Staiger JF, Sakmann B, Feldmeyer D (2008) Efficient recruitment of layer 2/3 interneurons by layer 4 input in single columns of rat somatosensory cortex. J Neurosci 28:8273–8284
Hirsch JA (1995) Synaptic integration in layer IV of the ferret striate cortex. J Physiol-London 483, 183–199
Hirsch JA, Martinez LM, Alonso JM, Desai K, Pillai C, Pierre C (2002) Synaptic physiology of the flow of information in the cat’s visual cortex in vivo. J Physiol-London 540:335–350
Hoeflinger BF, Bennett-Clarke CA, Chiaia NL, Killackey HP, Rhoades RW (1995) Patterning of local intracortical projections within the vibrissae representation of rat primary somatosensory cortex. J Comp Neurol 354:551–563
Hoffer ZS, Hoover JE, Alloway KD (2003) Sensorimotor corticocortical projections from rat barrel cortex have an anisotropic organization that facilitates integration of inputs from whiskers in the same row. J Comp Neurol 466:525–544
Hubel DH, Wiesel TN (1959) Receptive fields of single neurones in the cat’s striate cortex. J Physiol-London 148:574–591
Ito M (1992) Simultaneous visualization of cortical barrels and horseradish peroxidase-injected layer 5b vibrissa neurones in the rat. J Physiol-London 454:247–265
Karube F, Kubota Y, Kawaguchi Y (2004) Axon branching and synaptic bouton phenotypes in GABAergic nonpyramidal cell subtypes. J Neurosci 24:2853–2865
Katz LC, Gilbert CD, Wiesel TN (1989) Local circuits and ocular dominance columns in monkey striate cortex. J Neurosci 9:1389–1399
Kawaguchi Y, Kubota Y (1997) GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb Cortex 7:476–486
Koester HJ, Johnston D (2005) Target cell-dependent normalization of transmitter release at neocortical synapses. Science 308:863–866
Kozloski J, Hamzei-Sichani F, Yuste R (2001) Stereotyped position of local synaptic targets in neocortex. Science 293:868–872
Kumar P, Ohana O (2008) Inter- and intralaminar subcircuits of excitatory and inhibitory neurons in layer 6a of the rat barrel cortex. J Neurophysiol 100:1909–1922
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
Larkum ME, Zhu JJ (2002) Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo. J Neurosci 22:6991–7005
Larkum ME, Zhu JJ, Sakmann B (1999) A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398:338–341
Larsen DD, Callaway EM (2006) Development of layer-specific axonal arborizations in mouse primary somatosensory cortex. J Comp Neurol 494:398–414
Larsen DD, Wickersham IR, Callaway EM (2007) Retrograde tracing with recombinant rabies virus reveals correlations between projection targets and dendritic architecture in layer 5 of mouse barrel cortex. Front Neural Circuits 1:5
Le Bé JV, Silberberg G, Wang Y, Markram H (2007) Morphological, electrophysiological, and synaptic properties of corticocallosal pyramidal cells in the neonatal rat neocortex. Cereb Cortex 17:2204–2213
Lee CC, Sherman SM (2008) Synaptic Properties of Thalamic and Intracortical Inputs to Layer 4 of the First- and Higher-Order Cortical Areas in the Auditory and Somatosensory Systems. J Neurophysiol 100:317–326
Lefort S, Tomm C, Floyd Sarria JC, Petersen CC (2009) The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex. Neuron 61:301–316
Lorente de Nó R (1949) Cerebral cortex: architecture, intracortical connections, motor projections. In: Fulton JF (ed) Physiology of the nervous system, 3rd edn. Oxford University Press, London, pp 288–313
Lübke J, Egger V, Sakmann B, Feldmeyer D (2000a) Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex. J Neurosci 20:5300–5311
Lübke J, Feldmeyer D (2007) Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex. Brain Struct Funct 212:3–17
Lübke J, Feldmeyer D, Silver RA, Sakmann B (2000b) Morphology of synaptic connections between spiny layer 4 neurones and layer 2/3 pyramidal cells in rat barrel cortex. Eur J Neurosci 12:14–14
Lübke J, Roth A, Feldmeyer D, Sakmann B (2003) Morphometric analysis of the columnar innervation domain of neurons connecting layer 4 and layer 2/3 of juvenile rat barrel cortex. Cereb Cortex 13:1051–1063
Lund JS, Wu Q, Hadingham PT, Levitt JB (1995) Cells and circuits contributing to functional properties in area V1 of macaque monkey cerebral cortex: bases for neuroanatomically realistic models. J Anat 187:563–581
Luskin MB, Shatz CJ (1985) Neurogenesis of the cat’s primary visual cortex. J Comp Neurol 242:611–631
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-London 556:601–622
Marín-Padilla M (1971) Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis domestica) A Golgi study. I. The primordial neocortical organization. Z Anat Entwicklungsgesch 134:117–145
Marín-Padilla M (1978) Dual origin of the mammalian neocortex and evolution of the cortical plate. Anat Embryol (Berl) 152:109–126
Markram H (1997) A network of tufted layer 5 pyramidal neurons. Cereb Cortex 7:523–533
Markram H, Lübke J, Frotscher M, Roth A, Sakmann B (1997) Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J Physiol-London 500:409–440
Markram H, Wang Y, Tsodyks M (1998) Differential signaling via the same axon of neocortical pyramidal neurons. Proc Natl Acad Sci USA 95:5323–5328
Martin KA, Whitteridge D (1984) Form, function and intracortical projections of spiny neurones in the striate visual cortex of the cat. J Physiol 353:463–504
Micheva KD, Beaulieu C (1995) Postnatal development of GABA neurons in the rat somatosensory barrel cortex: a quantitative study. Eur J Neurosci 7:419–430
Miller MW (1988) Maturation of rat visual cortex: IV. The generation, migration, morphogenesis, and connectivity of atypically oriented pyramidal neurons. J Comp Neurol 274:387–405
Mountcastle VB (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J Neurophysiol 20:408–434
Muly EC, Fitzpatrick D (1992) The morphological basis for binocular and ON/OFF convergence in tree shrew striate cortex. J Neurosci 12:1319–1334
Peters A, Walsh TM (1972) A study of the organization of apical dendrites in the somatic sensory cortex of the rat. J Comp Neurol 144:253–268
Petreanu L, Mao T, Sternson SM, Svoboda K (2009) The subcellular organization of neocortical excitatory connections. Nature 457:1142–1145
Porter JT, Johnson CK, Agmon A (2001) Diverse types of interneurons generate thalamus-evoked feedforward inhibition in the mouse barrel cortex. J Neurosci 21:2699–2710
Porter LL, Sakamoto K (1988) Organization and synaptic relationships of the projection from the primary sensory to the primary motor cortex in the cat. J Comp Neurol 271:387–396
Porter LL, Sakamoto T, Asanuma H (1990) Morphological and physiological identification of neurons in the cat motor cortex which receive direct input from the somatic sensory cortex. Exp Brain Res 80:209–212
Ramón y Cajal S (1904) Textura del Sistema Nervioso del Hombre y de los Vertebrados. Imprenta de Nicolás Moya, Madrid
Reblet C, Blanco I, Mendizabal-Zubiaga J, Gutierrez-Ibarluzea I, Bueno-Lopez JL (1996) Development of inverted cells in infragranular layers of the rabbit visual cortex. Int J Dev Biol Suppl 1:145S–146S
Reep RL (2000) Cortical layer VII and persistent subplate cells in mammalian brains. Brain Behav Evol 56:212–234
Reep RL, Goodwin GS (1988) Layer VII of rodent cerebral cortex. Neurosci Lett 90:15–20
Reyes A, Lujan R, Rozov A, Burnashev N, Somogyi P, Sakmann B (1998) Target-cell-specific facilitation and depression in neocortical circuits. Nat Neurosci 1:279–285
Schubert D, Kotter 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
Schubert D, Kotter R, Zilles K, Luhmann HJ, Staiger JF (2003) Cell type-specific circuits of cortical layer IV spiny neurons. J Neurosci 23:2961–2970
Shepherd GM, Stepanyants A, Bureau I, Chklovskii D, Svoboda K (2005) Geometric and functional organization of cortical circuits. Nat Neurosci 8:782–790
Shepherd GM, 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
Silver RA, Lübke J, Sakmann B, Feldmeyer D (2003) High-probability uniquantal transmission at excitatory synapses in barrel cortex. Science 302:1981–1984
Soltesz I (2006) Diversity in the neuronal machine: order and variability in interneuronal microcircuits. Oxford University Press, Oxford, New York
Somogyi P, Freund TF, Cowey A (1982) The axo-axonic interneuron in the cerebral cortex of the rat, cat and monkey. Neuroscience 7:2577–2607
Somogyi P, Tamás G, Lujan R, Buhl EH (1998) Salient features of synaptic organisation in the cerebral cortex. Brain Res Brain Res Rev 26:113–135
Staiger JF, Flagmeyer I, Schubert D, Zilles K, Kotter 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
Tamás G, Buhl EH, Lőrincz A, Somogyi P (2000) Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Nat Neurosci 3:366–371
Tamás G, Lőrincz A, Simon A, Szabadics J (2003) Identified sources and targets of slow inhibition in the neocortex. Science 299:1902–1905
Tamás G, Somogyi P, Buhl EH (1998) Differentially interconnected networks of GABAergic interneurons in the visual cortex of the cat. J Neurosci 18:4255–4270
Thomson AM, Bannister AP (2003) Interlaminar connections in the neocortex. Cereb Cortex 13:5–14
Tömböl T (1984) Layer VI cells. In: Peters A, Jones EG (eds) Cerebral cortex. Plenum Press, New York, London, pp. 479–519
Tömböl T, Hajdu F, Somogyi G (1975) Identification of the Golgi picture of the layer VI cortic-geniculate projection neurons. Exp Brain Res 24:107–110
Ts’o DY, Gilbert CD, Wiesel TN (1986) Relationships between horizontal interactions and functional architecture in cat striate cortex as revealed by cross-correlation analysis. J Neurosci 6:1160–1170
Valverde F (1986) Intrinsic neocortical organization: some comparative aspects. Neuroscience 18:1–23
Vandevelde IL, Duckworth E, Reep RL (1996) Layer VII and the gray matter trajectories of corticocortical axons in rats. Anat Embryol (Berl) 194:581–593
Watakabe A, Ichinohe N, Ohsawa S, Hashikawa T, Komatsu Y, Rockland KS, Yamamori T (2007) Comparative analysis of layer-specific genes in mammalian neocortex. Cereb Cortex 17:1918–1933
Winkelmann E, Brauer K, Berger U (1975) Zur columnaren Organisation von Pyramidenzellen im visuellen Cortex der Albinoratte. Z Mikrosk Anat Forsch 89:239–256
Wise SP, Jones EG (1976) The organization and postnatal development of the commissural projection of the rat somatic sensory cortex. J Comp Neurol 168:313–343
Woolsey TA, Van der Loos H (1970) The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res 17:205–242
Yabuta NH, Callaway EM (1998) Functional streams and local connections of layer 4C neurons in primary visual cortex of the macaque monkey. J Neurosci 18:9489–9499
Yabuta NH, Sawatari A, Callaway EM (2001) Two functional channels from primary visual cortex to dorsal visual cortical areas. Science 292:297–300
Zhang ZW, Deschênes M (1997) Intracortical axonal projections of lamina VI cells of the primary somatosensory cortex in the rat: a single-cell labeling study. J Neurosci 17:6365–6379
Zhang ZW, Deschênes M (1998) Projections to layer VI of the posteromedial barrel field in the rat: a reappraisal of the role of corticothalamic pathways. Cereb Cortex 8:428–436
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Lübke, J.H., Feldmeyer, D. (2010). The Axon of Excitatory Neurons in the Neocortex: Projection Patterns and Target Specificity. In: Feldmeyer, D., Lübke, J. (eds) New Aspects of Axonal Structure and Function. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1676-1_9
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