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.

Driving fast-spiking cells induces gamma rhythm and controls sensory responses


Cortical gamma oscillations (20-80 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.

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: AAV DIO ChR2-mCherry gives Cre-dependent and cell-type-specific expression of light-activated channels in vivo.
Figure 2: Light-evoked activity in FS-PV + inhibitory interneurons suppresses sensory processing in nearby excitatory neurons.
Figure 3: FS inhibitory interneurons generate gamma oscillations in the local cortical network.
Figure 4: Gamma oscillations gate sensory responses of excitatory neurons.


  1. Berger, H. On the electroencephalogram of man. Electroencephalogr. Clin. Neurophysiol. 28 (Suppl.) 37–74 (1969)

    Google Scholar 

  2. Steriade, M. Grouping of brain rhythms in corticothalamic systems. Neuroscience 137, 1087–1106 (2006)

    CAS  Article  Google Scholar 

  3. Traub, R. D., Whittington, M. A., Stanford, I. M. & Jefferys, J. G. A mechanism for generation of long-range synchronous fast oscillations in the cortex. Nature 383, 621–624 (1996)

    ADS  CAS  Article  Google Scholar 

  4. Traub, R. D., Jefferys, J. G. & Whittington, M. A. Simulation of gamma rhythms in networks of interneurons and pyramidal cells. J. Comput. Neurosci. 4, 141–150 (1997)

    CAS  Article  Google Scholar 

  5. Whittington, M. A., Traub, R. D. & Jefferys, J. G. Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation. Nature 373, 612–615 (1995)

    ADS  CAS  Article  Google Scholar 

  6. Whittington, M. A., Faulkner, H. J., Doheny, H. C. & Traub, R. D. Neuronal fast oscillations as a target site for psychoactive drugs. Pharmacol. Ther. 86, 171–190 (2000)

    CAS  Article  Google Scholar 

  7. Deans, M. R., Gibson, J. R., Sellitto, C., Connors, B. W. & Paul, D. L. Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 31, 477–485 (2001)

    CAS  Article  Google Scholar 

  8. Galarreta, M. & Hestrin, S. A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature 402, 72–75 (1999)

    ADS  CAS  Article  Google Scholar 

  9. Hasenstaub, A. et al. Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks. Neuron 47, 423–435 (2005)

    CAS  Article  Google Scholar 

  10. Wang, X. J. & Buzsaki, G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J. Neurosci. 16, 6402–6413 (1996)

    CAS  Article  Google Scholar 

  11. Borgers, C., Epstein, S. & Kopell, N. J. Background gamma rhythmicity and attention in cortical local circuits: a computational study. Proc. Natl Acad. Sci. USA 102, 7002–7007 (2005)

    ADS  Article  Google Scholar 

  12. Whittington, M. A., Traub, R. D., Faulkner, H. J., Stanford, I. M. & Jefferys, J. G. Recurrent excitatory postsynaptic potentials induced by synchronized fast cortical oscillations. Proc. Natl Acad. Sci. USA 94, 12198–12203 (1997)

    ADS  CAS  Article  Google Scholar 

  13. Gray, C. M. & Singer, W. Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex. Proc. Natl Acad. Sci. USA 86, 1698–1702 (1989)

    ADS  CAS  Article  Google Scholar 

  14. Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001)

    ADS  CAS  Article  Google Scholar 

  15. Fries, P., Nikolic, D. & Singer, W. The gamma cycle. Trends Neurosci. 30, 309–316 (2007)

    CAS  Article  Google Scholar 

  16. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005)

    CAS  Article  Google Scholar 

  17. Deisseroth, K. et al. Next-generation optical technologies for illuminating genetically targeted brain circuits. J. Neurosci. 26, 10380–10386 (2006)

    CAS  Article  Google Scholar 

  18. Hippenmeyer, S. et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 3, e159 (2005)

    Article  Google Scholar 

  19. Kuhlman, S. J. & Huang, Z. J. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression. PLoS ONE 3, e2005 (2008)

    ADS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  21. Ren, J. Q., Aika, Y., Heizmann, C. W. & Kosaka, T. Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with special reference to GABAergic neurons and parvalbumin-containing neurons. Exp. Brain Res. 92, 1–14 (1992)

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  23. Cauli, B. et al. Molecular and physiological diversity of cortical nonpyramidal cells. J. Neurosci. 17, 3894–3906 (1997)

    CAS  Article  Google Scholar 

  24. Zeng, H. et al. Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. Cell 107, 617–629 (2001)

    CAS  Article  Google Scholar 

  25. Hubbard, J. I., Llinas, R. & Quastel, D. M. J. Electrophysiological Analysis of Synaptic Transmission (The Camelot Press Ltd, 1969)

    Google Scholar 

  26. Borgers, C. & Kopell, N. Effects of noisy drive on rhythms in networks of excitatory and inhibitory neurons. Neural Comput. 17, 557–608 (2005)

    MathSciNet  Article  Google Scholar 

  27. Engel, A. K. & Singer, W. Temporal binding and the neural correlates of sensory awareness. Trends Cogn. Sci. 5, 16–25 (2001)

    Article  Google Scholar 

  28. Fries, P., Neuenschwander, S., Engel, A. K., Goebel, R. & Singer, W. Rapid feature selective neuronal synchronization through correlated latency shifting. Nature Neurosci. 4, 194–200 (2001)

    CAS  Article  Google Scholar 

  29. Burchell, T. R., Faulkner, H. J. & Whittington, M. A. Gamma frequency oscillations gate temporally coded afferent inputs in the rat hippocampal slice. Neurosci. Lett. 255, 151–154 (1998)

    CAS  Article  Google Scholar 

  30. Huber, D. et al. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451, 61–64 (2008)

    ADS  CAS  Article  Google Scholar 

  31. Orekhova, E. V. et al. Excess of high frequency electroencephalogram oscillations in boys with autism. Biol. Psychiatry 62, 1022–1029 (2007)

    Article  Google Scholar 

  32. Spencer, K. M., Niznikiewicz, M. A., Shenton, M. E. & McCarley, R. W. Sensory-evoked gamma oscillations in chronic schizophrenia. Biol. Psychiatry 63, 744–747 (2008)

    Article  Google Scholar 

  33. Uhlhaas, P. J., Haenschel, C., Nikolic, D. & Singer, W. The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia. Schizophr. Bull. 34, 927–943 (2008)

    Article  Google Scholar 

Download references


We are grateful to S. Arber for the PV-Cre mice, S. Tonegawa for the CW2 mice, and A. Bradshaw, C. Ruehlmann and S. Su for technical assistance. We thank members of the Boyden laboratory and J. Bernstein for help in setting up optical techniques. We thank members of the Tsai and Moore laboratories, D. Vierling-Claassen and M. J. Higley for discussions and comments on the paper. This study was supported by grants from Tom F. Petersen, the NIH and the NSF to C.I.M. and by the Simons Foundation Autism Research Initiative to L.-H.T. K.D. is supported by the NIH Pioneer Program. L.-H.T. is an investigator of the Howard Hughes Medical Institute. J.A.C. is supported by a K99 from the NIH/NEI, M.C. and K.M. by postdoctoral fellowships from the Knut och Alice Wallenberg Foundation, M.C. by a NARSAD Young Investigator Award, and F.Z. by an NIH NRSA.

Author Contributions J.A.C., M.C., K.M., L.-H.T. and C.I.M. designed the experiments. F.Z. and K.D. designed and cloned the AAV DIO ChR2-mCherry vector. M.C. and K.M. characterized the virus in vitro and in vivo and injected the animals. M.C. performed histological statistical analyses. J.A.C. performed and analysed the extracellular recordings. U.K. and J.A.C. performed the intracellular recordings. U.K. analysed the intracellular data. J.A.C., M.C., K.M., U.K., L.-H.T. and C.I.M. wrote the manuscript.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Karl Deisseroth, Li-Huei Tsai or Christopher I. Moore.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-10 with Legends and Supplementary Methods. (PDF 15074 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

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