Clonally related visual cortical neurons show similar stimulus feature selectivity

Abstract

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.

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Acknowledgements

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). https://doi.org/10.1038/nature11110

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