All-optical recreation of naturalistic neural activity with a multifunctional transgenic reporter mouse
Hayley A. Bounds,
Masato Sadahiro,
William D. Hendricks,
Marta Gajowa,
Karthika Gopakumar,
Daniel Quintana,
Bosiljka Tasic,
Tanya L. Daigle,
Hongkui Zeng,
Ian Antón Oldenburg,
Hillel Adesnik
Affiliations
Hayley A. Bounds
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; The Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA
Masato Sadahiro
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
William D. Hendricks
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Marta Gajowa
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Karthika Gopakumar
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Daniel Quintana
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Bosiljka Tasic
Allen Institute for Brain Science, Seattle, WA, USA
Tanya L. Daigle
Allen Institute for Brain Science, Seattle, WA, USA
Hongkui Zeng
Allen Institute for Brain Science, Seattle, WA, USA
Ian Antón Oldenburg
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Corresponding author
Hillel Adesnik
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; The Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Corresponding author
Summary: Determining which features of the neural code drive behavior requires the ability to simultaneously read out and write in neural activity patterns with high precision across many neurons. All-optical systems that combine two-photon calcium imaging and targeted photostimulation enable the activation of specific, functionally defined groups of neurons. However, these techniques are unable to test how patterns of activity across a population contribute to computation because of an inability to both read and write cell-specific firing rates. To overcome this challenge, we make two advances: first, we introduce a genetic line of mice for Cre-dependent co-expression of a calcium indicator and a potent soma-targeted microbial opsin. Second, using this line, we develop a method for read-out and write-in of precise population vectors of neural activity by calibrating the photostimulation to each cell. These advances offer a powerful and convenient platform for investigating the neural codes of computation and behavior.
