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Nat Neurosci. 2018 Jun;21(6):881-893. doi: 10.1038/s41593-018-0139-8. Epub 2018 Apr 30.

Precise multimodal optical control of neural ensemble activity.

Author information

1
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
2
Department of Electrical Engineering & Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
3
Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA.
4
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
5
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA, USA. hadesnik@berkeley.edu.
6
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA. hadesnik@berkeley.edu.

Abstract

Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 × 550 × 100-µm3 volume of brain tissue. This approach allows the synthesis and editing of complex neural activity patterns needed to gain insight into the principles of neural codes.

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