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Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons

Nature Neuroscience volume 16, pages 1068–1076 (2013)Cite this article

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Abstract

Cortical inhibitory neurons contact each other to form a network of inhibitory synaptic connections. Our knowledge of the connectivity pattern underlying this inhibitory network is, however, still incomplete. Here we describe a simple and complementary interaction scheme between three large, molecularly distinct interneuron populations in mouse visual cortex: parvalbumin-expressing interneurons strongly inhibit one another but provide little inhibition to other populations. In contrast, somatostatin-expressing interneurons avoid inhibiting one another yet strongly inhibit all other populations. Finally, vasoactive intestinal peptide–expressing interneurons preferentially inhibit somatostatin-expressing interneurons. This scheme occurs in supragranular and infragranular layers, suggesting that inhibitory networks operate similarly at the input and output of the visual cortex. Thus, as the specificity of connections between excitatory neurons forms the basis for the cortical canonical circuit, the scheme described here outlines a standard connectivity pattern among cortical inhibitory neurons.

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Figure 1: Three non-overlapping Cre lines.
Figure 2: Five molecularly distinct interneuron categories defined by scRT-PCR.
Figure 3: Individual neuronal contributions of the three interneuron classes onto pyramidal cells.
Figure 4: Pvalb cells mainly inhibit one another.
Figure 5: Sst cells inhibit all other categories but one another.
Figure 6: Vip cells preferentially inhibit Sst cells.
Figure 7: Comparing individual neuronal contributions among cortical interneurons.

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Acknowledgements

We thank J. Evora for help with genotyping and mouse husbandry, M. Chan for immunohistochemical labeling, J. Isaacson for critical reading of the manuscript and the members of the Scanziani and Isaacson laboratories for advice during the course of the study. This work was supported in part by grants from the National Alliance for Research on Schizophrenia and Depression and US National Institutes of Health (NS047101). C.K.P. was supported by a European Molecular Biology Organization long-term fellowship (EMBO LTF 1114_2009) and the Howard Hughes Medical Institute. M.X. was supported by a fellowship from Jane Coffin Childs Memorial Fund for Medical Research. M.S. was supported by the Gatsby charitable foundation and the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, USA

    Carsten K Pfeffer & Massimo Scanziani

  2. Neurobiology Section and Department of Neuroscience, Center for Neural Circuits and Behavior, University of California San Diego, La Jolla, California, USA

    Carsten K Pfeffer, Mingshan Xue & Massimo Scanziani

  3. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

    Miao He & Z Josh Huang

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Contributions

C.K.P. and M.S. designed the study. C.K.P. conducted all experiments and analysis. M.X. contributed paired-recordings. Z.J.H. and M.H. contributed Vip-IRES-Cre mice. C.K.P. and M.S. wrote the paper.

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Correspondence to Carsten K Pfeffer or Massimo Scanziani.

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Pfeffer, C., Xue, M., He, M. et al. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons. Nat Neurosci 16, 1068–1076 (2013). https://doi.org/10.1038/nn.3446

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