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J Neurophysiol. 2016 Jul 1;116(1):135-52. doi: 10.1152/jn.00226.2016. Epub 2016 Apr 13.

Voltage imaging to understand connections and functions of neuronal circuits.

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Stem Cell Institute, Institute for Systems Genomics, UConn Health, Farmington, Connecticut;
Department of Physiology, Brain Research New Zealand, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; and.
Division of Brain Sciences, Department of Medicine and Centre for Neurotechnology, Institute of Biomedical Engineering, Imperial College London, London, United Kingdom


Understanding of the cellular mechanisms underlying brain functions such as cognition and emotions requires monitoring of membrane voltage at the cellular, circuit, and system levels. Seminal voltage-sensitive dye and calcium-sensitive dye imaging studies have demonstrated parallel detection of electrical activity across populations of interconnected neurons in a variety of preparations. A game-changing advance made in recent years has been the conceptualization and development of optogenetic tools, including genetically encoded indicators of voltage (GEVIs) or calcium (GECIs) and genetically encoded light-gated ion channels (actuators, e.g., channelrhodopsin2). Compared with low-molecular-weight calcium and voltage indicators (dyes), the optogenetic imaging approaches are 1) cell type specific, 2) less invasive, 3) able to relate activity and anatomy, and 4) facilitate long-term recordings of individual cells' activities over weeks, thereby allowing direct monitoring of the emergence of learned behaviors and underlying circuit mechanisms. We highlight the potential of novel approaches based on GEVIs and compare those to calcium imaging approaches. We also discuss how novel approaches based on GEVIs (and GECIs) coupled with genetically encoded actuators will promote progress in our knowledge of brain circuits and systems.


GECI; GEVI; membrane voltage; neurophysiology; optical imaging

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