Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution

By Xue Han, Ed Boyden. PLoS ONE, 2007

631 citations recorded by the source corpus.

The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells.

Subfields: Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/c4661b97c58d5c7e570e7e3f46df9860f0c9f16c

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In Cellular and Molecular Neuroscience

Citations in the corpus

Spatiotemporal Control of Cell Signalling Using A Light-Switchable Protein Interaction (2009, background): “PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.”
Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins (2011, background): “(iv) Finally the nature of the action spectrum will dictate feasibility of combining with other light-activated reagents in the same preparatio”
Optogenetic investigation of neural circuits underlying brain disease in animal models (2012, background): “— which enables action potential elicitation to be time-locked to light pulses — or halorhodopsin (NpHR”
An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology (2007, methodology): “It has also been suggested from work in cell culture that this method could be used to desynchronize or inhibit neurons [68].”
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing (2012, neutral): “(c) Quantified response of population bursting from CA1 (n = 4 experiments) during four intervals: light-off control, the first (0) and final (4) minute of a 5-min exposure to white light, and 5 min after light exposure (recovery).”
The Development and Application of Optogenetics (2011, methodology): “…with NpHR was shown to operate well in freely moving worms (Zhang et al. 2007a), mammalian brain slices (Zhang et al. 2007a), and cultured neurons (Han & Boyden 2007, Zhang et al. 2007a), several years passed before final validation of this (or any) inhibitory optogenetic tool was obtained by…”
Molecular and cellular approaches for diversifying and extending optogenetics. (2010, background): “…activity (precisely timed hyperpolarization) can be achieved via expression of the Natronomonas halorhodopsin (NpHR) in vivo (Zhang et al., 2007a; Han and Boyden, 2007; Gradinaru et al., 2008); this halorhodopsin was selected for its step-like and highly stable photocurrents compared with other…”
Genetic dissection of neural circuits. (2008, neutral): “In neurons expressing NpHR, pulses of bright yellow light induce rapid hyperpolarization that can abolish action potential generation (Han and Boyden, 2007; Zhang et al., 2007).”