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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.

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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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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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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).

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