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The columnar and laminar organization of inhibitory connections to neocortical excitatory cells

Nature Neuroscience volume 14, pages 100–107 (2011)Cite this article

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Abstract

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.

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Figure 1: ChR2 expression in GABAergic interneurons.
Figure 2: Genetically targeted photostimulation of GABAergic interneurons.
Figure 3: Optogenetic mapping of inhibitory connectivity.
Figure 4: Horizontal (columnar) organization of inhibitory connections.
Figure 5: Vertical (laminar) organization of inhibitory connections.
Figure 6: Area-specific differences in the laminar organization of inhibitory connections.
Figure 7: Cell-specific differences in the laminar organization of inhibitory connections.

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Acknowledgements

We thank P. Chambon (Université de Strasbourg), F. Costantini (Columbia University), S. Dymecki (Harvard Medical School), G. Nagel (Universität Würzburg) and P. Soriano (Mount Sinai School of Medicine) for plasmids and T. Ellender, M. Kohl, K. Lamsa, W. Nissen, T. Nottoli, R. Roorda, Y. Tan and L. Upton for assistance and/or discussions. This work was supported by the UK Medical Research Council (G.M.), the US National Institutes of Health (G.M.), the Dana Foundation (G.M.), the US Office of Naval Research (G.M.), the Boehringer Ingelheim Fonds (D.K.) and the Christopher Welch Scholarship Fund (D.K.).

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

    Dennis Kätzel, Christina Buetfering & Gero Miesenböck

  2. Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA

    Boris V Zemelman, Markus Wölfel & Gero Miesenböck

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  1. Dennis Kätzel
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Contributions

D.K. and G.M. designed the study, analyzed the results and wrote the paper. B.V.Z. generated the R26∷ChR2-EGFP and Gad2∷CreERT2 targeting constructs. C.B. and M.W. helped with the initial characterization of the resulting mouse knock-in lines. D.K. performed all experiments.

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Correspondence to Gero Miesenböck.

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Kätzel, D., Zemelman, B., Buetfering, C. et al. The columnar and laminar organization of inhibitory connections to neocortical excitatory cells. Nat Neurosci 14, 100–107 (2011). https://doi.org/10.1038/nn.2687

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