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The emergence of functional microcircuits in visual cortex

Nature volume 496, pages 96–100 (2013)Cite this article

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Abstract

Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured1,2,3,4 and excitatory neurons form subnetworks that process related sensory information5,6. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience—a process that may be facilitated by early electrical coupling between neuronal subsets7,8,9—and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.

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Figure 1: Responses of L2/3 pyramidal cells in mouse visual cortex are highly feature selective at eye opening.
Figure 2: Functionally specific connectivity between L2/3 pyramidal cells is not apparent at eye opening.
Figure 3: Developmental elimination of recurrent connections between non-responsive neurons.
Figure 4: Feedforward input structure determines the functional organization of recurrent connectivity.

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Acknowledgements

We thank C. Akerman, D. Attwell, R. Froemke, M. Hausser, C. Levelt, C. Lohmann, T. Margrie, J. Sjostrom and members of the Mrsic-Flogel laboratory for advice and comments on the manuscript. We thank D. Farquarson, D. Halpin, A. Hogben of the University College London machine shop for custom parts. The work was supported by the Wellcome Trust (T.D.M.-F., S.B.H., C.B.), the Medical Research Council (L.C.), the European Research Council and the 7th Framework of European Commission ‘EuroV1sion’ grant (T.D.M.-F.), and the Swiss National Science Foundation (C.C., grant no. PA00P3_139703).

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Author notes

  1. Jan Antolik

    Present address: Present address: Unité de Neuroscience Information et Complexité, UPR 3293 CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.,

  2. Ho Ko, Lee Cossell, Sonja B. Hofer and Thomas D. Mrsic-Flogel: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Physiology and Pharmacology, University College London, 21 University Street, London WC1E 6DE, UK,

    Ho Ko, Lee Cossell, Chiara Baragli, Jan Antolik, Sonja B. Hofer & Thomas D. Mrsic-Flogel

  2. Center for Theoretical Neuroscience, Columbia University, 1051 Riverside Drive, Unit 87 Kolb Research Annex, New York, New York 10032, USA,

    Claudia Clopath

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Contributions

H.K. and S.B.H. performed the in vivo and in vitro experiments and data analysis. S.B.H. performed the RF mapping experiments, and L.C. analysed the RF data with help from J.A. L.C., C.B. and C.C. extended the network model originally developed by C.C. H.K., L.C., S.B.H. and T.D.M.-F. wrote the manuscript. All authors discussed the data and commented on the manuscript.

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Correspondence to Sonja B. Hofer or Thomas D. Mrsic-Flogel.

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Ko, H., Cossell, L., Baragli, C. et al. The emergence of functional microcircuits in visual cortex. Nature 496, 96–100 (2013). https://doi.org/10.1038/nature12015

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