All-Optical Electrophysiology in hiPSC-Derived Neurons With Synthetic Voltage Sensors

Francesca Puppo; Sanaz Sadegh; Cleber A Trujillo; Martin Thunemann; Evan P Campbell; Matthieu Vandenberghe; Xiwei Shan; Ibrahim A Akkouh; Evan W Miller; Brenda L Bloodgood; Gabriel A Silva; Anders M Dale; Gaute T Einevoll; Srdjan Djurovic; Ole A Andreassen; Alysson R Muotri; Anna Devor

doi:10.3389/fncel.2021.671549

All-Optical Electrophysiology in hiPSC-Derived Neurons With Synthetic Voltage Sensors

Front Cell Neurosci. 2021 May 28:15:671549. doi: 10.3389/fncel.2021.671549. eCollection 2021.

Authors

Francesca Puppo¹, Sanaz Sadegh², Cleber A Trujillo^{1

3}, Martin Thunemann⁴, Evan P Campbell⁵, Matthieu Vandenberghe⁶, Xiwei Shan^{1

3}, Ibrahim A Akkouh⁶, Evan W Miller⁷, Brenda L Bloodgood⁵, Gabriel A Silva⁸, Anders M Dale⁹, Gaute T Einevoll^{10

11}, Srdjan Djurovic^{12

13}, Ole A Andreassen⁶, Alysson R Muotri^{1

3

14

15}, Anna Devor^{4

16}

Affiliations

¹ Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, United States.
² Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
³ Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, United States.
⁴ Department of Biomedical Engineering, Boston University, Boston, MA, United States.
⁵ Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA, United States.
⁶ Division of Mental Health and Addiction, Oslo University Hospital, NORMENT, KG Jebsen Centre for Neurodevelopmental Disorders, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States.
⁸ Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States.
⁹ Department of Radiology, University of California, San Diego, La Jolla, CA, United States.
¹⁰ Faculty of Science and Technology, Norwegian University of Life Sciences, Ås, Norway.
¹¹ Department of Physics, University of Oslo, Oslo, Norway.
¹² Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
¹³ NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
¹⁴ Kavli Institute for Brain and Mind and Halıcıoglu Data Science Institute, University of California, San Diego, La Jolla, CA, United States.
¹⁵ Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA, United States.
¹⁶ Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.

Abstract

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.

Keywords: BeRST-1; optogenetics; phenotyping; stem cells; voltage imaging.

Abstract

Grants and funding