Voltage imaging to understand connections and functions of neuronal circuits

Abstract

Antic SD, Empson RM, Knöpfel T. Voltage imaging to understand connections and functions of neuronal circuits. J Neurophysiol 116: 135-152, 2016. First published April 13, 2016 doi:10.1152/jn.00226.2016.-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 THE IMPORTANCE OF STUDYING VOLTAGE SIGNALS within biological organisms was realized as far back as the eighteenth century by the scientist Luigi Galvani (1737-1798). Galvani proposed that electrical forces power movement in animals, which he termed "animal electricity"; thus all life is electrical (Bresadola 2008). Galvani's seminal work inspired the invention by Alessandro Volta of the first electric battery, used by Michael Faraday and other pioneers of physics. In a straightforward manner, biology gave birth to the modern physics of electricity and electronic circuits. This enormous contribution of biology to the modern world is often overlooked.Electrophysiological measures, instigated by Galvani, Volta, Helmholtz, Bernstein, Adrian, Renshaw, Curtis, Cole, Hodgkin, Huxley, and others, have become a key methodology in neuroscience because fluctuations of membrane potential both are the physical means of signal transmission among the elements of a neuronal circuit and comprise the substrate of fast information processing (integration) in the brain. It is therefore indubitable that detecting and recording voltage changes from neurons in living animals and linking these signals to cognitive and emotional tasks is required for understanding the mammalian brain. In this review we explore the idea that the brain is essentially an electric information processing device with simultaneous multisite processing and that, consequently, simult...

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Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity

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