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Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution
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Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution
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Journal Article
Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution
2007
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Action Potentials - physiology
/ Anesthesiology and Pain Management/Anesthetic Mechanisms
/ Animals
/ Biophysics/Experimental Biophysical Methods
/ Biophysics/Membrane Proteins and Energy Transduction
/ Brain
/ Cell Biology/Neuronal and Glial Cell Biology
/ Cell Biology/Neuronal Signaling Mechanisms
/ Chloride
/ Codons
/ Color
/ Disease
/ Epilepsy
/ Light
/ Neurons
/ Neuroscience/Animal Cognition
/ Neuroscience/Cognitive Neuroscience
/ Neuroscience/Theoretical Neuroscience
/ Pain
/ Pharmacology/Drug Development
/ Physiology/Neuronal Signaling Mechanisms
/ Proteins
/ Rats
/ Sinuses
