A Light-Gated, Potassium-Selective Glutamate Receptor for the Optical Inhibition of Neuronal Firing

Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
Nature Neuroscience (Impact Factor: 16.1). 08/2010; 13(8):1027-32. DOI: 10.1038/nn.2589
Source: PubMed


Genetically targeted light-activated ion channels and pumps make it possible to determine the role of specific neurons in neuronal circuits, information processing and behavior. We developed a K+-selective ionotropic glutamate receptor that reversibly inhibits neuronal activity in response to light in dissociated neurons and brain slice and also reversibly suppresses behavior in zebrafish. The receptor is a chimera of the pore region of a K+-selective bacterial glutamate receptor and the ligand-binding domain of a light-gated mammalian kainate receptor. This hyperpolarizing light-gated channel, HyLighter, is turned on by a brief light pulse at one wavelength and turned off by a pulse at a second wavelength. The control is obtained at moderate intensity. After optical activation, the photocurrent and optical silencing of activity persists in the dark for extended periods. The low light requirement and bi-stability of HyLighter represent advantages for the dissection of neural circuitry.

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Available from: Claire Wyart, Oct 04, 2015
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    • "For example, a new kind of light controllable rapidly reversible TrpA1 ligand, optovin, was recently discovered in just this way (Kokel et al., 2013a). Several novel light activated molecules have been developed using zebrafish behavioral readouts (Szobota et al., 2007; Janovjak et al., 2010; Levitz et al., 2013). This suggests that truly novel compounds are waiting to be found, if only we use the right methods to look for them. "
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    • "VI. COMBINING OPTOGENETICS WITH TWO-PHOTON MICROSCOPY As discussed earlier, methods for guiding spatial delivery of single-photon light excitation have been used to improve the precision of optogenetic modulation [69], [131]–[138]. Light localization with higher precision can be achieved using multiphoton excitation microscopy. "
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    • "Our architecture builds on these pioneering studies by enabling ion channel activity to be dynamically controlled over rapid timescales. Finally, a third line of past inquiry utilizes light-responsive, externally added chemical ligands anchored to specific sites engineered into ion channels13–19, enabling fast induction and reversal, by modulating the concentration of the ligand relative to the ion channel surface. Our current methodology extends these ideas by being fully genetically encoded, eliminating the need for exogenous chemical application. "
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