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Millisecond-timescale, genetically targeted optical control of neural activity

Abstract

Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

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Figure 1: ChR2 enables light-driven neuron spiking.
Figure 2: Realistic spike trains driven by series of light pulses.
Figure 3: Frequency dependence of coupling between light input and spike output.
Figure 4: Simulated and natural synaptic transmission evoked via ChR2.
Figure 5: Basal and dynamic electrical properties of neurons expressing ChR2.

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Acknowledgements

We would like to thank L. Meltzer and N. Adeishvili for experimental assistance; C. Niell, C. Chan and J.P. Levy for helpful discussions and D. Ollig for technical help. E.B. and G.N. are supported by the Max-Planck-Society and acknowledge a grant from the German Research Foundation (DFG) in the research unit 472 (Molekulare Bioenergetik). E.S.B. is supported by the Helen Hay Whitney Foundation, the Dan David Prize Foundation, and National Institute on Deafness and Other Communication Disorders, and F.Z. is supported by a US National Institutes of Health predoctoral fellowship. K.D. is supported by the National Institute of Mental Health, the Stanford Department of Bioengineering, the Stanford Department of Psychiatry and Behavioral Sciences, the Neuroscience Institute at Stanford, the National Alliance for Research On Schizophrenia and Depression and the Culpeper, Klingenstein, Whitehall, McKnight, and Albert Yu and Mary Bechmann Foundations.

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Correspondence to Karl Deisseroth.

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Boyden, E., Zhang, F., Bamberg, E. et al. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8, 1263–1268 (2005). https://doi.org/10.1038/nn1525

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