High-speed mapping of synaptic connectivity using photostimulation in channelrhodopsin-2 transgenic mice

Wang, H., Peca, J., Matsusaki, M., Matsusaki, K., Noguchi, J., Qiu, L., Wang, D., Zhang, F., Boyden, E. S., Deisseroth, K., Kasai, H., Hall, W. C., Feng, G., Augustine, G. J. (2007) High-speed mapping of synaptic connectivity using photostimulation in channelrhodopsin-2 transgenic mice, Proceedings of the National Academy of Sciences 104(19):8143-848.

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To permit rapid optical control of brain activity, we have engineered multiple lines of transgenic mice that express the light-activated cation channel Channelrhodopsin-2 (ChR2) in subsets of neurons. Illumination of ChR2-positive neurons in brain slices produced photocurrents that generated action potentials within milliseconds and with precisely timed latencies. The number of light-evoked action potentials could be controlled by varying either the amplitude or duration of illumination. Furthermore, the frequency of light-evoked action potentials could be precisely controlled up to 30 Hz. Photostimulation also could evoke synaptic transmission between neurons, and, by scanning with a small laser light spot, we were able to map the spatial distribution of synaptic circuits connecting neurons within living cerebral cortex. We conclude that ChR2 is a genetically based photostimulation technology that permits analysis of neural circuits with high spatial and temporal resolution in transgenic mammals.

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Understanding, and simulating, the brain

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