Letter | Published:

Cortical interneurons that specialize in disinhibitory control

Nature volume 503, pages 521524 (28 November 2013) | Download Citation


This article has been updated


In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control1,2,3,4,5,6,7. A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation8,9. Although several interneuron populations are known to target other interneurons to varying degrees10,11,12,13,14,15, little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively3,6,16,17. During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.

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Change history

  • 30 October 2013

    Figure 1 in the HTML version was corrupted. This has now been updated.

  • 27 November 2013

    Figure 3b and its legend were corrected and the number 98 was changed to 97 in three places on page 2.


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We are grateful to B. Mensh, S. Ranade, N. Spruston and A. M. Zador for comments and discussions; S. Ranade and R. Eifert for assistance for microdrive design; S. G. Koh, A. Reid, H. Li and Y. Kim for help with experimental setup; A. M. Zador for use of in vitro electrophysiology equipment; B. Burbach for technical assistance; and J. Kuhl for help with figures. This research was supported by grants from NIH NINDS R01NS075531, the Klingenstein, John Merck, and Sloan Foundations to A.K. and from NIH NIMH U01MH078844 to Z.J.H. B.H. received support from the Swartz Foundation and Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development. D.K. received support from The Robert Lee and Clara Guthrie Patterson Trust Postdoctoral Fellowship and Human Frontier Science Program.

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  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA

    • Hyun-Jae Pi
    • , Balázs Hangya
    • , Duda Kvitsiani
    • , Joshua I. Sanders
    • , Z. Josh Huang
    •  & Adam Kepecs
  2. Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary

    • Balázs Hangya


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H.-J.P., B.H. and A.K. designed the experiments. H.-J.P. and B.H. performed the experiments and analysed data. D.K. set up in vivo optogenetics-assisted recordings. J.I.S. designed custom behaviour and stimulation systems for the behavioural task. Z.J.H. provided the VIP-IRES-Cre mouse line. H.-J.P., B.H. and A.K. wrote the manuscript with comments from Z.J.H., J.S. and D.K.

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The authors declare no competing financial interests.

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Correspondence to Adam Kepecs.

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