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

Nature Neuroscience volume 18, pages 1780–1788 (2015)Cite this article

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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.

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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.

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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).

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Authors and Affiliations

  1. Department of Molecular Physiology, Kyushu University Graduate School of Medical Sciences, Maidashi, Higashi-Ku, Fukuoka, Japan.,

    Kenta M Hagihara, Tomonari Murakami, Takashi Yoshida & Kenichi Ohki

  2. CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan

    Takashi Yoshida, Yoshiaki Tagawa & Kenichi Ohki

  3. Department of Biophysics, Kyoto University Graduate School of Science, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto, Japan.,

    Yoshiaki Tagawa

  4. Department of Physiology, The University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan.,

    Kenichi Ohki

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  1. Kenta M Hagihara
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  2. Tomonari Murakami
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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.

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Correspondence to Yoshiaki Tagawa or Kenichi Ohki.

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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

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