Clonally related visual cortical neurons show similar stimulus feature selectivity


A fundamental feature of the mammalian neocortex is its columnar organization1. In the visual cortex, functional columns consisting of neurons with similar orientation preferences have been characterized extensively2,3,4, but how these columns are constructed during development remains unclear5. The radial unit hypothesis6 posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fibre during corticogenesis7 provide the basis for functional columns in adult neocortex1. However, a direct correspondence between the ontogenetic and functional columns has not been demonstrated8. Here we show that, despite the lack of a discernible orientation map in mouse visual cortex4,9,10, sister neurons in the same radial clone exhibit similar orientation preferences. Using a retroviral vector encoding green fluorescent protein to label radial clones of excitatory neurons, and in vivo two-photon calcium imaging to measure neuronal response properties, we found that sister neurons preferred similar orientations whereas nearby non-sister neurons showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 (also known as Gjb2) or by daily administration of a gap junction blocker, carbenoxolone, during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons11, our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.

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Figure 1: Two-photon imaging of clonally related sister cells and nearby layer 2/3 neurons.
Figure 2: Orientation and direction preference of sister neurons.
Figure 3: Effect of expressing dominant-negative mutant of Cx26 in sister neurons.


  1. 1

    Mountcastle, V. B. The columnar organization of the neocortex. Brain 120, 701–722 (1997)

    Article  Google Scholar 

  2. 2

    Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J. Physiol. (Lond.) 160, 106–154 (1962)

    CAS  Article  Google Scholar 

  3. 3

    Bonhoeffer, T. & Grinvald, A. Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. Nature 353, 429–431 (1991)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Ohki, K., Chung, S., Ch’ng, Y. H., Kara, P. & Reid, R. C. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433, 597–603 (2005)

    ADS  CAS  Article  Google Scholar 

  5. 5

    White, L. E. & Fitzpatrick, D. Vision and cortical map development. Neuron 56, 327–338 (2007)

    CAS  Article  Google Scholar 

  6. 6

    Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Noctor, S. C., Flint, A. C., Weissman, T. A., Dammerman, R. S. & Kriegstein, A. R. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Horton, J. C. & Adams, D. L. The cortical column: a structure without a function. Phil. Trans. R. Soc. Lond. B 360, 837–862 (2005)

    Article  Google Scholar 

  9. 9

    Schuett, S., Bonhoeffer, T. & Hubener, M. Mapping retinotopic structure in mouse visual cortex with optical imaging. J. Neurosci. 22, 6549–6559 (2002)

    CAS  Article  Google Scholar 

  10. 10

    Ko, H. et al. Functional specificity of local synaptic connections in neocortical networks. Nature 473, 87–91 (2011)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Yu, Y. C., Bultje, R. S., Wang, X. & Shi, S. H. Specific synapses develop preferentially among sister excitatory neurons in the neocortex. Nature 458, 501–504 (2009)

    ADS  CAS  Article  Google Scholar 

  12. 12

    Cepko, C. L. et al. Studies of cortical development using retrovirus vectors. Cold Spring Harb. Symp. Quant. Biol. 55, 265–278 (1990)

    CAS  Article  Google Scholar 

  13. 13

    Polleux, F., Dehay, C. & Kennedy, H. The timetable of laminar neurogenesis contributes to the specification of cortical areas in mouse isocortex. J. Comp. Neurol. 385, 95–116 (1997)

    CAS  Article  Google Scholar 

  14. 14

    Denk, W., Strickler, J. H. & Webb, W. W. 2-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl Acad. Sci. USA 100, 7319–7324 (2003)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Walsh, C. & Cepko, C. L. Clonal dispersion in proliferative layers of developing cerebral cortex. Nature 362, 632–635 (1993)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Rochefort, N. L. et al. Development of direction selectivity in mouse cortical neurons. Neuron 71, 425–432 (2011)

    CAS  Article  Google Scholar 

  18. 18

    Yuste, R., Peinado, A. & Katz, L. C. Neuronal domains in developing neocortex. Science 257, 665–669 (1992)

    ADS  CAS  Article  Google Scholar 

  19. 19

    Nadarajah, B., Jones, A. M., Evans, W. H. & Parnavelas, J. G. Differential expression of connexins during neocortical development and neuronal circuit formation. J. Neurosci. 17, 3096–3111 (1997)

    CAS  Article  Google Scholar 

  20. 20

    Beahm, D. L. et al. Mutation of a conserved threonine in the third transmembrane helix of α- and β-connexins creates a dominant-negative closed gap junction channel. J. Biol. Chem. 281, 7994–8009 (2006)

    CAS  Article  Google Scholar 

  21. 21

    Rouan, F. et al. Trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. J. Cell Sci. 114, 2105–2113 (2001)

    CAS  PubMed  Google Scholar 

  22. 22

    Elias, L. A. & Kriegstein, A. R. Gap junctions: multifaceted regulators of embryonic cortical development. Trends Neurosci. 31, 243–250 (2008)

    CAS  Article  Google Scholar 

  23. 23

    Kandler, K. & Katz, L. C. Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication. J. Neurosci. 18, 1419–1427 (1998)

    CAS  Article  Google Scholar 

  24. 24

    Peinado, A., Yuste, R. & Katz, L. C. Extensive dye coupling between rat neocortical neurons during the period of circuit formation. Neuron 10, 103–114 (1993)

    CAS  Article  Google Scholar 

  25. 25

    Song, S., Sjostrom, P. J., Reigl, M., Nelson, S. & Chklovskii, D. B. Highly nonrandom features of synaptic connectivity in local cortical circuits. PLoS Biol. 3, e68 (2005)

    Article  Google Scholar 

  26. 26

    Yoshimura, Y., Dantzker, J. L. & Callaway, E. M. Excitatory cortical neurons form fine-scale functional networks. Nature 433, 868–873 (2005)

    ADS  CAS  Article  Google Scholar 

  27. 27

    Rockel, A. J., Hiorns, R. W. & Powell, T. P. The basic uniformity in structure of the neocortex. Brain 103, 221–244 (1980)

    CAS  Article  Google Scholar 

  28. 28

    Niell, C. M. & Stryker, M. P. Highly selective receptive fields in mouse visual cortex. J. Neurosci. 28, 7520–7536 (2008)

    CAS  Article  Google Scholar 

  29. 29

    Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006)

    ADS  CAS  Article  Google Scholar 

  30. 30

    Koulakov, A. A. & Chklovskii, D. B. Orientation preference patterns in mammalian visual cortex: a wire length minimization approach. Neuron 29, 519–527 (2001)

    CAS  Article  Google Scholar 

  31. 31

    van Praag, H. et al. Functional neurogenesis in the adult hippocampus. Nature 415, 1030–1034 (2002)

    ADS  CAS  Article  Google Scholar 

  32. 32

    Garaschuk, O., Milos, R. I. & Konnerth, A. Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo. Nature Protocols 1, 380–386 (2006)

    CAS  Article  Google Scholar 

  33. 33

    Pologruto, T., Sabatini, B. & Svoboda, K. ScanImage: Flexible software for operating laser scanning microscopes. Biomed. Eng. Online 2, 13 (2003)

    Article  Google Scholar 

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This work was supported by National Institutes of Health (NIH) grant R01 EY018861 and NSF grant 22250400-42533 (to Y.D.), and NIH grants R01 DA024681 and R21NS072483 (to S.-H.S.). We thank L. E. White and S. D. Van Hooser for comments on the manuscript, A. Kwan and S. D. Van Hooser for help with two-photon imaging techniques and analysis and Y. Gu for help in making retroviruses.

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Y.L. performed the two-photon imaging experiments and data analysis. H.L., Y.L. and P.-l.C. performed in utero virus injection. S.G., H.X. and S.-H.S. provided the viral vectors. Y.L., H.L. and Y.D. designed the experiments and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Yang Dan.

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The authors declare no competing financial interests.

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Li, Y., Lu, H., Cheng, P. et al. Clonally related visual cortical neurons show similar stimulus feature selectivity. Nature 486, 118–121 (2012).

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