Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Activation of specific interneurons improves V1 feature selectivity and visual perception

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

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.

References

  1. Markram, H. et al. Interneurons of the neocortical inhibitory system. Nature Rev. Neurosci. 5, 793–807 (2004)

    Article  CAS  Google Scholar 

  2. Xu, X. M., Roby, K. D. & Callaway, E. M. Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells. J. Comp. Neurol. 518, 389–404 (2010)

    Article  Google Scholar 

  3. Ascoli, G. A. et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nature Rev. Neurosci. 9, 557–568 (2008)

    Article  CAS  Google Scholar 

  4. Blanche, T. J., Spacek, M. A., Hetke, J. F. & Swindale, N. V. Polytrodes: high-density silicon electrode arrays for large-scale multiunit recording. J. Neurophysiol. 93, 2987–3000 (2005)

    Article  Google Scholar 

  5. Du, J. G. et al. High-resolution three-dimensional extracellular recording of neuronal activity with microfabricated electrode arrays. J. Neurophysiol. 101, 1671–1678 (2009)

    Article  Google Scholar 

  6. Deisseroth, K. Optogenetics. Nature Methods 8, 26–29 (2011)

    Article  CAS  Google Scholar 

  7. Chow, B. Y. et al. High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463, 98–102 (2010)

    Article  ADS  CAS  Google Scholar 

  8. Zhang, F. et al. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nature Protocols 5, 439–456 (2010)

    Article  CAS  Google Scholar 

  9. Sohal, V. S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009)

    Article  ADS  CAS  Google Scholar 

  10. Cardin, J. A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009)

    Article  ADS  CAS  Google Scholar 

  11. Toledo-Rodriguez, M. et al. Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex. Cereb. Cortex 14, 1310–1327 (2004)

    Article  Google Scholar 

  12. Kerlin, A. M., Andermann, M. L., Berezovskii, V. K. & Reid, R. C. Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex. Neuron 67, 858–871 (2010)

    Article  CAS  Google Scholar 

  13. Ma, W. P. et al. Visual representations by cortical somatostatin inhibitory neurons–selective but with weak and delayed responses. J. Neurosci. 30, 14371–14379 (2010)

    Article  CAS  Google Scholar 

  14. Tsien, J. Z. et al. Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87, 1317–1326 (1996)

    Article  CAS  Google Scholar 

  15. Dávid, C., Schleicher, A., Zuschratter, W. & Staiger, J. F. The innervation of parvalbumin-containing interneurons by VIP-immunopositive interneurons in the primary somatosensory cortex of the adult rat. Eur. J. Neurosci. 25, 2329–2340 (2007)

    Article  Google Scholar 

  16. Ayaz, A. & Chance, F. S. Gain modulation of neuronal responses by subtractive and divisive mechanisms of inhibition. J. Neurophysiol. 101, 958–968 (2009)

    Article  Google Scholar 

  17. Mehaffey, W. H., Doiron, B., Maler, L. & Turner, R. W. Deterministic multiplicative gain control with active dendrites. J. Neurosci. 25, 9968–9977 (2005)

    Article  CAS  Google Scholar 

  18. Kang, K. J., Shapley, R. M. & Sompolinsky, H. Information tuning of populations of neurons in primary visual cortex. J. Neurosci. 24, 3726–3735 (2004)

    Article  CAS  Google Scholar 

  19. Schoups, A., Vogels, R., Qian, N. & Orban, G. Practising orientation identification improves orientation coding in V1 neurons. Nature 412, 549–553 (2001)

    Article  ADS  CAS  Google Scholar 

  20. Andermann, M. L. K. e. r. l. i. n. A. M. &. R. e. i. d. R. C. Chronic cellular imaging of mouse visual cortex during operant behavior and passive viewing. Front. Cell. Neurosci. 4, 3 (2010)

    PubMed  PubMed Central  Google Scholar 

  21. Sillito, A. M. Effectiveness of bicuculline as an antagonist of GABA and visually evoked inhibition in the cat’s striate cortex. J. Physiol. (Lond.) 250, 287–304 (1975)

    Article  CAS  Google Scholar 

  22. Nelson, S., Toth, L., Sheth, B. & Sur, M. Orientation selectivity of cortical neurons during intracellular blockade of inhibition. Science 265, 774–777 (1994)

    Article  ADS  CAS  Google Scholar 

  23. Atallah, B. V., Bruns, W., Carandini, M. & Scanziani, M. Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron 73, 159–170 (2012)

    Article  CAS  Google Scholar 

  24. Chen, Y. et al. Task difficulty modulates the activity of specific neuronal populations in primary visual cortex. Nature Neurosci. 11, 974–982 (2008)

    Article  CAS  Google Scholar 

  25. Mitchell, J. F., Sundberg, K. A. & Reynolds, J. H. Differential attention-dependent response modulation across cell classes in macaque visual area V4. Neuron 55, 131–141 (2007)

    Article  CAS  Google Scholar 

  26. Ferster, D. & Miller, K. D. Neural mechanisms of orientation selectivity in the visual cortex. Annu. Rev. Neurosci. 23, 441–471 (2000)

    Article  CAS  Google Scholar 

  27. Runyan, C. A. et al. Response features of parvalbumin-expressing interneurons suggest precise roles for subtypes of inhibition in visual cortex. Neuron 67, 847–857 (2010)

    Article  CAS  Google Scholar 

  28. Troyer, T. W., Krukowski, A. E., Priebe, N. J. & Miller, K. D. Contrast-invariant orientation tuning in cat visual cortex: thalamocortical input tuning and correlation-based intracortical connectivity. J. Neurosci. 18, 5908–5927 (1998)

    Article  CAS  Google Scholar 

  29. Di Cristo, G. et al. Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs. Nature Neurosci. 7, 1184–1186 (2004)

    Article  CAS  Google Scholar 

  30. Hensch, T. K. Critical period plasticity in local cortical circuits. Nature Rev. Neurosci. 6, 877–888 (2005)

    Article  CAS  Google Scholar 

  31. Maheshri, N. et al. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nature Biotechnol. 24, 198–204 (2006)

    Article  CAS  Google Scholar 

  32. Hazan, L. et al. Klusters, NeuroScope, NDManager: a free software suite for neurophysiological data processing and visualization. J. Neurosci. Methods 155, 207–216 (2006)

    Article  Google Scholar 

  33. Harris, K. D. et al. Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. J. Neurophysiol. 84, 401–414 (2000)

    Article  CAS  Google Scholar 

  34. Schmitzer-Torbert, N. et al. Quantitative measures of cluster quality for use in extracellular recordings. Neuroscience 131, 1–11 (2005)

    Article  CAS  Google Scholar 

  35. O’Connor, D. H. et al. Vibrissa-based object localization in head-fixed mice. J. Neurosci. 30, 1947–1967 (2010)

    Article  Google Scholar 

  36. Green, D. M. & Swets, J. A. Signal Detection Theory and Psychophysics (Wiley, 1966)

    Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Yang Dan.

Ethics declarations

Competing interests

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)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11312

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing