Neuronal activity is not required for the initial formation and maturation of visual selectivity

Abstract

Neuronal activity is important for the functional refinement of neuronal circuits in the early visual system. At the level of the cerebral cortex, however, it is still unknown whether the formation of fundamental functions such as orientation selectivity depends on neuronal activity, as it has been difficult to suppress activity throughout development. Using genetic silencing of cortical activity starting before the formation of orientation selectivity, we found that the orientation selectivity of neurons in the mouse visual cortex formed and matured normally despite a strong suppression of both spontaneous and visually evoked activity throughout development. After the orientation selectivity formed, the distribution of the preferred orientations of neurons was reorganized. We found that this process required spontaneous activity, but not visually evoked activity. Thus, the initial formation and maturation of orientation selectivity is largely independent of neuronal activity, and the initial selectivity is subsequently modified depending on neuronal activity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Kir2.1 expression strongly suppressed the synchronous spontaneous activity.
Figure 2: Kir2.1 expression strongly suppressed the visual response.
Figure 3: Activity suppression by Kir2.1 did not prevent the maturation of orientation and direction selectivity.
Figure 4: Cell-attached recordings of neurons whose activity were suppressed by Kir2.1 during developmental stage.
Figure 5: The formation of orientation selectivity and the equalization of orientation bias had different time courses.
Figure 6: Layer 4 neurons show normally tuned orientation and direction selectivity just after eye-opening, in spite of suppression of spontaneous activity and deprivation of visually evoked activity.
Figure 7: Activity suppression by Kir2.1 prevented the equalization in the orientation and direction bias.

References

  1. 1

    Hubel, D.H. & Wiesel, T.N. Receptive fields of cells in striate cortex of very young, visually inexperienced kittens. J. Neurophysiol. 26, 994–1002 (1963).

    CAS  PubMed  Google Scholar 

  2. 2

    Wiesel, T.N. & Hubel, D.H. Ordered arrangement of orientation columns in monkeys lacking visual experience. J. Comp. Neurol. 158, 307–318 (1974).

    CAS  Google Scholar 

  3. 3

    Miller, K.D., Erwin, E. & Kayser, A. Is the development of orientation selectivity instructed by activity? J. Neurobiol. 41, 44–57 (1999).

    CAS  PubMed  Google Scholar 

  4. 4

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

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Yu, Y.C. et al. Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly. Nature 486, 113–117 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Ohtsuki, G. et al. Similarity of visual selectivity among clonally related neurons in visual cortex. Neuron 75, 65–72 (2012).

    CAS  PubMed  Google Scholar 

  7. 7

    Penn, A.A., Riquelme, P.A., Feller, M.B. & Shatz, C.J. Competition in retinogeniculate patterning driven by spontaneous activity. Science 279, 2108–2112 (1998).

    CAS  Google Scholar 

  8. 8

    Huberman, A.D., Feller, M.B. & Chapman, B. Mechanisms underlying development of visual maps and receptive fields. Annu. Rev. Neurosci. 31, 479–509 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Cang, J. et al. Development of precise maps in visual cortex requires patterned spontaneous activity in the retina. Neuron 48, 797–809 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Huberman, A.D., Speer, C.M. & Chapman, B. Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1. Neuron 52, 247–254 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Crair, M.C., Gillespie, D.C. & Stryker, M.P. The role of visual experience in the development of columns in cat visual cortex. Science 279, 566–570 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Sengpiel, F., Stawinski, P. & Bonhoeffer, T. Influence of experience on orientation maps in cat visual cortex. Nat. Neurosci. 2, 727–732 (1999).

    CAS  PubMed  Google Scholar 

  13. 13

    Kreile, A.K., Bonhoeffer, T. & Hubener, M. Altered visual experience induces instructive changes of orientation preference in mouse visual cortex. J. Neurosci. 31, 13911–13920 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

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

    CAS  Google Scholar 

  15. 15

    Kang, E. et al. Visual acuity development and plasticity in the absence of sensory experience. J. Neurosci. 33, 17789–17796 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Chapman, B. & Stryker, M.P. Development of orientation selectivity in ferret visual cortex and effects of deprivation. J. Neurosci. 13, 5251–5262 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    White, L.E., Coppola, D.M. & Fitzpatrick, D. The contribution of sensory experience to the maturation of orientation selectivity in ferret visual cortex. Nature 411, 1049–1052 (2001).

    CAS  PubMed  Google Scholar 

  18. 18

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

    CAS  PubMed  Google Scholar 

  19. 19

    Garaschuk, O., Linn, J., Eilers, J. & Konnerth, A. Large-scale oscillatory calcium waves in the immature cortex. Nat. Neurosci. 3, 452–459 (2000).

    CAS  PubMed  Google Scholar 

  20. 20

    Rochefort, N.L. et al. Sparsification of neuronal activity in the visual cortex at eye-opening. Proc. Natl. Acad. Sci. USA 106, 15049–15054 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Allene, C. & Cossart, R. Early NMDA receptor-driven waves of activity in the developing neocortex: physiological or pathological network oscillations? J. Physiol. (Lond.) 588, 83–91 (2010).

    CAS  Google Scholar 

  22. 22

    Ackman, J.B., Burbridge, T.J. & Crair, M.C. Retinal waves coordinate patterned activity throughout the developing visual system. Nature 490, 219–225 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Siegel, F., Heimel, J.A., Peters, J. & Lohmann, C. Peripheral and central inputs shape network dynamics in the developing visual cortex in vivo. Curr. Biol. 22, 253–258 (2012).

    CAS  PubMed  Google Scholar 

  24. 24

    Weliky, M. & Katz, L.C. Disruption of orientation tuning in visual cortex by artificially correlated neuronal activity. Nature 386, 680–685 (1997).

    CAS  PubMed  Google Scholar 

  25. 25

    Chiu, C. & Weliky, M. Spontaneous activity in developing ferret visual cortex in vivo. J. Neurosci. 21, 8906–8914 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Ko, H. et al. The emergence of functional microcircuits in visual cortex. Nature 496, 96–100 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Ko, H., Mrsic-Flogel, T.D. & Hofer, S.B. Emergence of feature-specific connectivity in cortical microcircuits in the absence of visual experience. J. Neurosci. 34, 9812–9816 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Kuhlman, S.J., Tring, E. & Trachtenberg, J.T. Fast-spiking interneurons have an initial orientation bias that is lost with vision. Nat. Neurosci. 14, 1121–1123 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Li, Y.T., Ma, W.P., Pan, C.J., Zhang, L.I. & Tao, H.W. Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity. J. Neurosci. 32, 3981–3991 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Wang, B.S., Feng, L., Liu, M., Liu, X. & Cang, J. Environmental enrichment rescues binocular matching of orientation preference in mice that have a precocious critical period. Neuron 80, 198–209 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Hoy, J.L. & Niell, C.M. Layer-specific refinement of visual cortex function after eye opening in the awake mouse. J. Neurosci. 35, 3370–3383 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Dräger, U.C. Receptive fields of single cells and topography in mouse visual cortex. J. Comp. Neurol. 160, 269–290 (1975).

    PubMed  Google Scholar 

  33. 33

    Mank, M. et al. A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Nat. Methods 5, 805–811 (2008).

    CAS  PubMed  Google Scholar 

  34. 34

    Girshick, A.R., Landy, M.S. & Simoncelli, E.P. Cardinal rules: visual orientation perception reflects knowledge of environmental statistics. Nat. Neurosci. 14, 926–932 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Coppola, D.M., Purves, H.R., McCoy, A.N. & Purves, D. The distribution of oriented contours in the real world. Proc. Natl. Acad. Sci. USA 95, 4002–4006 (1998).

    CAS  PubMed  Google Scholar 

  36. 36

    Coppola, D.M., White, L.E., Fitzpatrick, D. & Purves, D. Unequal representation of cardinal and oblique contours in ferret visual cortex. Proc. Natl. Acad. Sci. USA 95, 2621–2623 (1998).

    CAS  PubMed  Google Scholar 

  37. 37

    Johns, D.C., Marx, R., Mains, R.E., O′Rourke, B. & Marban, E. Inducible genetic suppression of neuronal excitability. J. Neurosci. 19, 1691–1697 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Mizuno, H., Hirano, T. & Tagawa, Y. Evidence for activity-dependent cortical wiring: formation of interhemispheric connections in neonatal mouse visual cortex requires projection neuron activity. J. Neurosci. 27, 6760–6770 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Niculescu, D. & Lohmann, C. Gap junctions in developing thalamic and neocortical neuronal networks. Cereb. Cortex 24, 3097–3106 (2013).

    PubMed  PubMed Central  Google Scholar 

  41. 41

    Yamada, A. et al. Role of pre- and postsynaptic activity in thalamocortical axon branching. Proc. Natl. Acad. Sci. USA 107, 7562–7567 (2010).

    CAS  PubMed  Google Scholar 

  42. 42

    Sohya, K., Kameyama, K., Yanagawa, Y., Obata, K. & Tsumoto, T. GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice. J. Neurosci. 27, 2145–2149 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Kerlin, A.M., Andermann, M.L., Berezovskii, V.K. & Reid, R.C. Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex. Neuron 67, 858–871 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Hofer, S.B. et al. Differential connectivity and response dynamics of excitatory and inhibitory neurons in visual cortex. Nat. Neurosci. 14, 1045–1052 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Hooks, B.M. & Chen, C. Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron 52, 281–291 (2006).

    CAS  PubMed  Google Scholar 

  46. 46

    Marshel, J.H., Kaye, A.P., Nauhaus, I. & Callaway, E.M. Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus. Neuron 76, 713–720 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Li, Y.T., Ibrahim, L.A., Liu, B.H., Zhang, L.I. & Tao, H.W. Linear transformation of thalamocortical input by intracortical excitation. Nat. Neurosci. 16, 1324–1330 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Cruz-Martín, A. et al. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex. Nature 507, 358–361 (2014).

    PubMed  PubMed Central  Google Scholar 

  49. 49

    Elstrott, J. et al. Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves. Neuron 58, 499–506 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Smith, G.B. & Fitzpatrick, D. Specifying cortical circuits: a role for cell lineage. Neuron 75, 4–5 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Shcherbo, D. et al. Bright far-red fluorescent protein for whole-body imaging. Nat. Methods 4, 741–746 (2007).

    CAS  PubMed  Google Scholar 

  52. 52

    Drobizhev, M., Makarov, N.S., Tillo, S.E., Hughes, T.E. & Rebane, A. Two-photon absorption properties of fluorescent proteins. Nat. Methods 8, 393–399 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Mizuno, H., Hirano, T. & Tagawa, Y. Pre-synaptic and post-synaptic neuronal activity supports the axon development of callosal projection neurons during different post-natal periods in the mouse cerebral cortex. Eur. J. Neurosci. 31, 410–424 (2010).

    PubMed  Google Scholar 

  54. 54

    Hagihara, K.M. & Ohki, K. Long-term down-regulation of GABA decreases orientation selectivity without affecting direction selectivity in mouse primary visual cortex. Front. Neural Circuits 7, 28 (2013).

    PubMed  PubMed Central  Google Scholar 

  55. 55

    Peirce, J.W. PsychoPy–Psychophysics software in Python. J. Neurosci. Methods 162, 8–13 (2007).

    PubMed  PubMed Central  Google Scholar 

  56. 56

    Helmchen, F., Imoto, K. & Sakmann, B. Ca2+ buffering and action potential-evoked Ca2+ signaling in dendrites of pyramidal neurons. Biophys. J. 70, 1069–1081 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Kitamura, K., Judkewitz, B., Kano, M., Denk, W. & Hausser, M. Targeted patch-clamp recordings and single-cell electroporation of unlabeled neurons in vivo. Nat. Methods 5, 61–67 (2008).

    CAS  PubMed  Google Scholar 

  58. 58

    Komai, S., Denk, W., Osten, P., Brecht, M. & Margrie, T.W. Two-photon targeted patching (TPTP) in vivo. Nat. Protoc. 1, 647–652 (2006).

    CAS  PubMed  Google Scholar 

  59. 59

    Glass, G.V., Peckham, P.D. & Sanders, J.R. Consequences of failure to meet the assumptions underlying the fixed effects analysis of variance and covariance. Rev. Educ. Res. 42, 237–288 (1972).

    Google Scholar 

Download references

Acknowledgements

We thank T. Yokomizo (Juntendo University) for help and advice on molecular biology works, such as plasmids construction, Y. Tezuka (Kyoto University) for sharing the information about Tet-gene expression system development and histology works, M.H. Histed (Harvard Medical School) for reading the manuscript, K. Kitamura (University of Yamanashi), M. Kano and A. Takeuchi (University of Tokyo) for showing cell-attached recordings, S. Kondo (Kyushu University) for electrophysiology set up, K. Hayashi (Kyushu University) for plasmids construction, A. Honda and Y. Sono (Kyushu University) for animal care and genotyping, T. Hirano (Kyoto University), all of the members of Ohki laboratory for support and discussion, and the Research Support Center, Graduate School of Medical Sciences, Kyushu University for technical support. This work was supported by grants from CREST-JST (to K.O. and Y.T.), JSPS KAKENHI (grant number 25221001 to K.O., 23500388 to Y.T.), JST, Strategic International Research Cooperative Program, SCIP (to K.O.), Grant-in-Aid for Scientific Research on Innovative Areas, “Glial assembly: a new regulatory machinery of brain function and disorders” (25117004 to K.O.) and “Neural Diversity and Neocortical Organization” (23123508 and 25123707 to Y.T.), grants from the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, and the Uehara Memorial Foundation (to T.Y.). A part of this work was carried out under the Brain/MINDS by the MEXT of Japan. K.M.H. was supported by Takeda Science Foundation. T. M. was supported by JSPS Research Fellowship for Young Scientists(201503597).

Author information

Affiliations

Authors

Contributions

K.M.H., Y.T. and K.O. designed the research. K.M.H. performed most of the experiments and analyzed the data. T.M. performed two-photon imaging experiments, cell-attached recording experiments and wide-field imaging experiments, and analyzed the wide-field imaging data. Y.T. designed and constructed plasmids, performed in utero electroporation, and helped K.M.H. for histology experiments. T.Y. performed two-photon imaging experiments and in utero electroporation. K.M.H., Y.T., T.Y. and K.O. wrote the manuscript. Y.T. and K.O. supervised the entire project. All of the authors discussed and commented on the manuscript.

Corresponding authors

Correspondence to Yoshiaki Tagawa or Kenichi Ohki.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–16 and Supplementary Table 1 (PDF 12777 kb)

Supplementary Methods Checklist (PDF 516 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hagihara, K., Murakami, T., Yoshida, T. et al. Neuronal activity is not required for the initial formation and maturation of visual selectivity. Nat Neurosci 18, 1780–1788 (2015). https://doi.org/10.1038/nn.4155

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing