Nature 459, 663-667 (4 June 2009) | doi:10.1038/nature08002; Received 12 January 2009; Accepted 1 April 2009; Published online 26 April 2009

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

Jessica A. Cardin1,2,7, Marie Carlén3,4,7, Konstantinos Meletis3,4, Ulf Knoblich1, Feng Zhang5, Karl Deisseroth5, Li-Huei Tsai3,4,6 & Christopher I. Moore1

  1. McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139, USA
  2. Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  3. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139, USA
  4. Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  5. Department of Bioengineering, Stanford University, Stanford, California 94305, USA
  6. Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA
  7. These authors contributed equally to this work.

Correspondence to: Karl Deisseroth5Li-Huei Tsai3,4,6Christopher I. Moore1 Correspondence and requests for materials should be addressed to C.I.M. (Email:, L.-H.T (Email: or K.D. (Email:


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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