Skip to main content

Thank you for visiting 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.

Inhibition dominates sensory responses in the awake cortex

A Corrigendum to this article was published on 10 July 2013

This article has been updated


The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition1,2,3,4. In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition5,6,7,8,9. These measurements, however, have all been made during anaesthesia, which strongly influences cortical state10 and therefore sensory processing7,11,12,13,14,15. The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses—and the underlying synaptic conductances—in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space16 and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances5,17 showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Spontaneous and evoked activity in the anaesthetized and awake visual cortex (V1).
Figure 2: Anaesthetized responses are long lasting regardless of cortical state.
Figure 3: Responses are spatiotemporally restricted during waking.
Figure 4: Visually evoked conductance is dominated by inhibition in awake V1.

Change history


  1. Isaacson, J. S. & Scanziani, M. How inhibition shapes cortical activity. Neuron 72, 231–243 (2011)

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  3. Wilson, N. R., Runyan, C. A., Wang, F. L. & Sur, M. Division and subtraction by distinct cortical inhibitory networks in vivo . Nature 488, 343–348 (2012)

    ADS  CAS  Article  Google Scholar 

  4. Lee, S. H. et al. Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488, 379–383 (2012)

    ADS  CAS  Article  Google Scholar 

  5. Borg-Graham, L., Monier, C. & Frégnac, Y. Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393, 369–373 (1998)

    ADS  CAS  Article  Google Scholar 

  6. Cardin, J. A., Kumbhani, R. D., Contreras, D. & Palmer, L. A. Cellular mechanisms of temporal sensitivity in visual cortex neurons. J. Neurosci. 30, 3652–3662 (2010)

    CAS  Article  Google Scholar 

  7. Haider, B. & McCormick, D. A. Rapid neocortical dynamics: cellular and network mechanisms. Neuron 62, 171–189 (2009)

    CAS  Article  Google Scholar 

  8. Mariño, J. et al. Invariant computations in local cortical networks with balanced excitation and inhibition. Nature Neurosci. 8, 194–201 (2005)

    ADS  Article  Google Scholar 

  9. Priebe, N. J. & Ferster, D. Inhibition, spike threshold, and stimulus selectivity in primary visual cortex. Neuron 57, 482–497 (2008)

    CAS  Article  Google Scholar 

  10. Harris, K. D. & Thiele, A. Cortical state and attention. Nature Rev. Neurosci. 12, 509–523 (2011)

    CAS  Article  Google Scholar 

  11. Crochet, S., Poulet, J. F., Kremer, Y. & Petersen, C. C. Synaptic mechanisms underlying sparse coding of active touch. Neuron 69, 1160–1175 (2011)

    CAS  Article  Google Scholar 

  12. Gilbert, C. D. & Sigman, M. Brain states: top-down influences in sensory processing. Neuron 54, 677–696 (2007)

    CAS  Article  Google Scholar 

  13. Goard, M. & Dan, Y. Basal forebrain activation enhances cortical coding of natural scenes. Nature Neurosci. 12, 1444–1449 (2009)

    CAS  Article  Google Scholar 

  14. Niell, C. M. & Stryker, M. P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010)

    CAS  Article  Google Scholar 

  15. Wörgötter, F. et al. State-dependent receptive-field restructuring in the visual cortex. Nature 396, 165–168 (1998)

    ADS  Article  Google Scholar 

  16. Bringuier, V., Chavane, F., Glaeser, L. & Frégnac, Y. Horizontal propagation of visual activity in the synaptic integration field of area 17 neurons. Science 283, 695–699 (1999)

    ADS  CAS  Article  Google Scholar 

  17. Wehr, M. & Zador, A. M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003)

    ADS  CAS  Article  Google Scholar 

  18. Steriade, M., Nunez, A. & Amzica, F. A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. 13, 3252–3265 (1993)

    CAS  Article  Google Scholar 

  19. Constantinople, C. M. & Bruno, R. M. Effects and mechanisms of wakefulness on local cortical networks. Neuron 69, 1061–1068 (2011)

    CAS  Article  Google Scholar 

  20. Steriade, M., Timofeev, I. & Grenier, F. Natural waking and sleep states: a view from inside neocortical neurons. J. Neurophysiol. 85, 1969–1985 (2001)

    CAS  Article  Google Scholar 

  21. Simons, D. J., Carvell, G. E., Hershey, A. E. & Bryant, D. P. Responses of barrel cortex neurons in awake rats and effects of urethane anesthesia. Exp. Brain Res. 91, 259–272 (1992)

    CAS  Article  Google Scholar 

  22. Liu, B. H. et al. Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells. Neuron 71, 542–554 (2011)

    CAS  Article  Google Scholar 

  23. Tan, A. Y., Brown, B. D., Scholl, B., Mohanty, D. & Priebe, N. J. Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex. J. Neurosci. 31, 12339–12350 (2011)

    CAS  Article  Google Scholar 

  24. Williams, S. R. & Mitchell, S. J. Direct measurement of somatic voltage clamp errors in central neurons. Nature Neurosci. 11, 790–798 (2008)

    CAS  Article  Google Scholar 

  25. Haider, B. et al. Synaptic and network mechanisms of sparse and reliable visual cortical activity during nonclassical receptive field stimulation. Neuron 65, 107–121 (2010)

    CAS  Article  Google Scholar 

  26. Ozeki, H., Finn, I. M., Schaffer, E. S., Miller, K. D. & Ferster, D. Inhibitory stabilization of the cortical network underlies visual surround suppression. Neuron 62, 578–592 (2009)

    CAS  Article  Google Scholar 

  27. Rudolph, M., Pospischil, M., Timofeev, I. & Destexhe, A. Inhibition determines membrane potential dynamics and controls action potential generation in awake and sleeping cat cortex. J. Neurosci. 27, 5280–5290 (2007)

    CAS  Article  Google Scholar 

  28. Swadlow, H. A. Thalamocortical control of feed-forward inhibition in awake somatosensory ‘barrel’ cortex. Phil. Trans. R. Soc. Lond. B 357, 1717–1727 (2002)

    Article  Google Scholar 

  29. Steriade, M., Amzica, F. & Nunez, A. Cholinergic and noradrenergic modulation of the slow (approximately 0.3 Hz) oscillation in neocortical cells. J. Neurophysiol. 70, 1385–1400 (1993)

    CAS  Article  Google Scholar 

  30. Arroyo, S., Bennett, C., Aziz, D., Brown, S. P. & Hestrin, S. Prolonged disynaptic inhibition in the cortex mediated by slow, non-α7 nicotinic excitation of a specific subset of cortical interneurons. J. Neurosci. 32, 3859–3864 (2012)

    CAS  Article  Google Scholar 

  31. Margrie, T. W., Brecht, M. & Sakmann, B. In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflügers Arch. 444, 491–498 (2002)

    CAS  Article  Google Scholar 

  32. Branco, T. & Häusser, M. Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69, 885–892 (2011)

    CAS  Article  Google Scholar 

  33. Cafaro, J. & Rieke, F. Noise correlations improve response fidelity and stimulus encoding. Nature 468, 964–967 (2010)

    ADS  CAS  Article  Google Scholar 

  34. Poo, C. & Isaacson, J. S. Odor representations in olfactory cortex: ‘sparse’ coding, global inhibition, and oscillations. Neuron 62, 850–861 (2009)

    CAS  Article  Google Scholar 

  35. Nowak, L. G., Azouz, R., Sanchez-Vives, M. V., Gray, C. M. & McCormick, D. A. Electrophysiological classes of cat primary visual cortical neurons in vivo as revealed by quantitative analyses. J. Neurophysiol. 89, 1541–1566 (2003)

    Article  Google Scholar 

  36. Haider, B., Duque, A., Hasenstaub, A. R., Yu, Y. & McCormick, D. A. Enhancement of visual responsiveness by spontaneous local network activity in vivo . J. Neurophysiol. 97, 4186–4202 (2007)

    Article  Google Scholar 

Download references


We thank T. Sato, A. Saleem and A. Ayaz for help with procedures; S. L. Smith, C. Schmidt-Hieber and K. Powell for advice on recordings, and A. Roth, M. Scanziani and D. McCormick for comments. We are grateful to the National Science Foundation, the European Research Council, the Wellcome Trust, the Medical Research Council and the Gatsby Charitable Foundation for financial support. M.C. holds the GlaxoSmithKline/Fight for Sight Chair in Visual Neuroscience.

Author information

Authors and Affiliations



B.H. performed the experiments. B.H. and M.C. performed the analyses. B.H., M.H. and M.C. designed the study and wrote the paper.

Corresponding author

Correspondence to Bilal Haider.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-11. Supplementary Figure 8 was corrected on 10 July 2013; see corrigendum linked to original manuscript for details. (PDF 936 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Haider, B., Häusser, M. & Carandini, M. Inhibition dominates sensory responses in the awake cortex. Nature 493, 97–100 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


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.


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