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      Optical Stimulation of Neurons

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          Abstract

          Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential.

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          Most cited references 177

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          Azobenzene photoswitches for biomolecules.

          The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references). This journal is © The Royal Society of Chemistry 2011
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            The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels.

            The mammalian sensory system is capable of discriminating thermal stimuli ranging from noxious cold to noxious heat. Principal temperature sensors belong to the TRP cation channel family, but the mechanisms underlying the marked temperature sensitivity of opening and closing ('gating') of these channels are unknown. Here we show that temperature sensing is tightly linked to voltage-dependent gating in the cold-sensitive channel TRPM8 and the heat-sensitive channel TRPV1. Both channels are activated upon depolarization, and changes in temperature result in graded shifts of their voltage-dependent activation curves. The chemical agonists menthol (TRPM8) and capsaicin (TRPV1) function as gating modifiers, shifting activation curves towards physiological membrane potentials. Kinetic analysis of gating at different temperatures indicates that temperature sensitivity in TRPM8 and TRPV1 arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. Our results suggest a simple unifying principle that explains both cold and heat sensitivity in TRP channels.
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              ReaChR: A red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation

              Channelrhodopsins are used to optogenetically depolarize neurons. We engineered a variant of channelrhodopsin, denoted Re d- a ctivatable Ch annel r hodopsin (ReaChR), that is optimally excited with orange to red light (λ ~ 590 to 630 nm) and offers improved membrane trafficking, higher photocurrents, and faster kinetics compared with existing red-shifted channelrhodopsins. Red light is more weakly scattered by tissue and absorbed less by blood than the blue to green wavelengths required by other channelrhodopsin variants. ReaChR expressed in vibrissa motor cortex was used to drive spiking and vibrissa motion in awake mice when excited with red light through intact skull. Precise vibrissa movements were evoked by expressing ReaChR in the facial motor nucleus in the brainstem and illuminating with red light through the external auditory canal. Thus, ReaChR enables transcranial optical activation of neurons in deep brain structures without the need to surgically thin the skull, form a transcranial window, or implant optical fibers.
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                Author and article information

                Journal
                Curr Mol Imaging
                Curr Mol Imaging
                CMI
                Current Molecular Imaging
                Bentham Science Publishers
                2211-5552
                2211-5544
                July 2014
                July 2014
                : 3
                : 2
                : 162-177
                Affiliations
                [1 ]Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Australia;
                [2 ]Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
                Author notes
                [* ]Address correspondence to this author at the Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Tel: +1-615-343-1911; E-mail: duco.jansen@ 123456vanderbilt.edu
                Article
                CMI-3-162
                10.2174/2211555203666141117220611
                4541079
                © 2014 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

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