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Activation of specific interneurons improves V1 feature selectivity and visual perception

Nature volume 488, pages 379–383 (2012)Cite this article

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Abstract

Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern1,2,3. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes4,5 and channelrhodopsin-2 (ChR2)-mediated optical activation6, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing7 of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.

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Figure 1: Optogenetic activation of PV + , SOM + and VIP + neurons and silencing of CAMKIIα + neurons.
Figure 2: PV + activation enhances V1 stimulus selectivity.
Figure 3: Effects of PV + and SOM + activation on F – I function.
Figure 4: PV + activation improves perceptual discrimination.

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Acknowledgements

We thank M. Goard, L. Pinto, M. Xu and M. Viesel for help with experimental setup, A. Kaluszka for help with data analysis and H. Alitto and M. Poo for discussion and comments on the manuscript. This work was supported by National Institutes of Health grants R01 EY018861 and PN2 EY018241 and National Science Foundation grant 22250400-42533.

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Authors and Affiliations

  1. Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, 94720, California, USA

    Seung-Hee Lee, Alex C. Kwan, Siyu Zhang, Victoria Phoumthipphavong, John G. Flannery & Yang Dan

  2. Howard Hughes Medical Institute, University of California, Berkeley, 94720, California, USA

    Seung-Hee Lee & Yang Dan

  3. Broad Fellows Program in Brain Circuitry, Kavli Nanoscience Institute, California Institute of Technology, Pasadena, 91125, California, USA

    Sotiris C. Masmanidis

  4. Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, New York, USA

    Hiroki Taniguchi & Z. Josh Huang

  5. Department of Bioengineering, Howard Hughes Medical Institute, Stanford University, Stanford, 94305, California, USA

    Feng Zhang & Karl Deisseroth

  6. Media Laboratory, Biological Engineering, Brain and Cognitive Sciences, and McGovern Institute, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Edward S. Boyden

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Contributions

S.-H.L. and Y.D. conceived and designed the experiments. S.-H.L. performed and organized all the experiments. A.C.K. developed the head-fixed awake mouse preparation and behavioural task setup. S.Z. performed whole-cell recording experiments. V.P. performed some of the virus injection and head-plate implant surgeries. J.G.F. supported viral vector preparation. S.C.M. manufactured silicon probe (type II). H.T. and Z.J.H. generated SOM-Cre and VIP-Cre mouse lines. E.S.B. generated the Arch–eGFP viral vector. F.Z. and K.D. developed the ChR2–eYFP viral vector. S.-H.L., A.K. and Y.D. analysed the data. S.-H.L. and Y.D. 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.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-8. (PDF 1101 kb)

Supplementary Movie 1

This movie file shows a head-fixed mouse performing visual discrimination. In it we see a PV-ChR2 mouse performing the hard discrimination task, in test blocks with Δθ = 90°, 60°, and 30°. The task design is shown in Fig. 4b. (MOV 13610 kb)

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Lee, SH., Kwan, A., Zhang, S. et al. Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488, 379–383 (2012). https://doi.org/10.1038/nature11312

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