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.
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Isaacson, J. S. & Scanziani, M. How inhibition shapes cortical activity. Neuron 72, 231–243 (2011)
Atallah, B. V., Bruns, W., Carandini, M. & Scanziani, M. Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron 73, 159–170 (2012)
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)
Lee, S. H. et al. Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488, 379–383 (2012)
Borg-Graham, L., Monier, C. & Frégnac, Y. Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393, 369–373 (1998)
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)
Haider, B. & McCormick, D. A. Rapid neocortical dynamics: cellular and network mechanisms. Neuron 62, 171–189 (2009)
Mariño, J. et al. Invariant computations in local cortical networks with balanced excitation and inhibition. Nature Neurosci. 8, 194–201 (2005)
Priebe, N. J. & Ferster, D. Inhibition, spike threshold, and stimulus selectivity in primary visual cortex. Neuron 57, 482–497 (2008)
Harris, K. D. & Thiele, A. Cortical state and attention. Nature Rev. Neurosci. 12, 509–523 (2011)
Crochet, S., Poulet, J. F., Kremer, Y. & Petersen, C. C. Synaptic mechanisms underlying sparse coding of active touch. Neuron 69, 1160–1175 (2011)
Gilbert, C. D. & Sigman, M. Brain states: top-down influences in sensory processing. Neuron 54, 677–696 (2007)
Goard, M. & Dan, Y. Basal forebrain activation enhances cortical coding of natural scenes. Nature Neurosci. 12, 1444–1449 (2009)
Niell, C. M. & Stryker, M. P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010)
Wörgötter, F. et al. State-dependent receptive-field restructuring in the visual cortex. Nature 396, 165–168 (1998)
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)
Wehr, M. & Zador, A. M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003)
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)
Constantinople, C. M. & Bruno, R. M. Effects and mechanisms of wakefulness on local cortical networks. Neuron 69, 1061–1068 (2011)
Steriade, M., Timofeev, I. & Grenier, F. Natural waking and sleep states: a view from inside neocortical neurons. J. Neurophysiol. 85, 1969–1985 (2001)
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)
Liu, B. H. et al. Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells. Neuron 71, 542–554 (2011)
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)
Williams, S. R. & Mitchell, S. J. Direct measurement of somatic voltage clamp errors in central neurons. Nature Neurosci. 11, 790–798 (2008)
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)
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)
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)
Swadlow, H. A. Thalamocortical control of feed-forward inhibition in awake somatosensory ‘barrel’ cortex. Phil. Trans. R. Soc. Lond. B 357, 1717–1727 (2002)
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)
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)
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)
Branco, T. & Häusser, M. Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69, 885–892 (2011)
Cafaro, J. & Rieke, F. Noise correlations improve response fidelity and stimulus encoding. Nature 468, 964–967 (2010)
Poo, C. & Isaacson, J. S. Odor representations in olfactory cortex: ‘sparse’ coding, global inhibition, and oscillations. Neuron 62, 850–861 (2009)
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)
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)
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.
The authors declare no competing financial interests.
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Haider, B., Häusser, M. & Carandini, M. Inhibition dominates sensory responses in the awake cortex. Nature 493, 97–100 (2013). https://doi.org/10.1038/nature11665
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