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From cudgel to scalpel: toward precise neural control with optogenetics

Nature Methods volume 8, pages 30–34 (2011)Cite this article

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Optogenetics is routinely used to activate and inactivate genetically defined neuronal populations in vivo. A second optogenetic revolution will occur when spatially distributed and sparse neural assemblies can be precisely manipulated in behaving animals.

A major goal of neuroscience is to link patterns of action potentials to behavior1. In a standard systems neuroscience experiment, neurophysiologists record from individual neurons or groups of neurons, ideally in behaving animals, and hunt for correlations between neural activity and specific perceptual, cognitive or motor functions. But the causal relationships between activity and behavior are rarely tested. A few celebrated experiments have used electrical microstimulation to bias, or even create, perceptual and motor behaviors, thus directly linking patterns of activity in specific brain regions to behavior1. However, the number of such experiments remains small, likely reflecting the complexity of neural circuits and the relative crudeness of the methods used.

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Figure 1: Manipulating neural assemblies with light.
Figure 2: Methods for two-photon photostimulation with ChR2.
Figure 3: Effects of dense packing of neural element on the precision of photostimulation.
Figure 4: Hypothetical scheme to manipulate distributed, sparse assemblies.

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Acknowledgements

We thank A. Vaziri, M. Hooks, D. Tank, P. Rickgauer and L. Petreanu for useful discussions, and M., Chklovskii for the reconstruction in Figure 3b.

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  1. Simon Peron and Karel Svoboda are at the Howard Hughes Medical Institute Janelia Farm Research Campus, Ashburn, Virginia, USA.,

    Simon Peron & Karel Svoboda

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Correspondence to Karel Svoboda.

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Peron, S., Svoboda, K. From cudgel to scalpel: toward precise neural control with optogenetics. Nat Methods 8, 30–34 (2011). https://doi.org/10.1038/nmeth.f.325

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