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

Nature volume 459, pages 663–667 (2009)Cite this article

Abstract

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.

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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.

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References

  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)

    Article  CAS  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)

    Article  ADS  CAS  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)

    Article  CAS  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)

    Article  ADS  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  ADS  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)

    Article  ADS  CAS  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)

    Article  ADS  CAS  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)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  Google Scholar 

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

    Article  CAS  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)

    Article  ADS  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)

    Article  CAS  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)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  MathSciNet  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  ADS  CAS  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

Acknowledgements

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.

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Author notes

  1. Jessica A. Cardin and Marie Carlén: These authors contributed equally to this work.

Authors and Affiliations

  1. McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139, USA,

    Jessica A. Cardin, Ulf Knoblich & Christopher I. Moore

  2. Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA,

    Jessica A. Cardin

  3. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, MIT, Cambridge, Massachusetts 02139, USA,

    Marie Carlén, Konstantinos Meletis & Li-Huei Tsai

  4. Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA ,

    Marie Carlén, Konstantinos Meletis & Li-Huei Tsai

  5. Department of Bioengineering, Stanford University, Stanford, California 94305, USA,

    Feng Zhang & Karl Deisseroth

  6. Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA ,

    Li-Huei Tsai

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  1. Jessica A. Cardin
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Correspondence to Karl Deisseroth, Li-Huei Tsai or Christopher I. Moore.

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Cardin, J., Carlén, M., Meletis, K. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009). https://doi.org/10.1038/nature08002

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