Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

When natural photoreception is disrupted, as in outer-retinal degenerative diseases, artificial stimulation of surviving nerve cells offers a potential strategy for bypassing compromised neural circuits. Recently, light-sensitive proteins that photosensitize quiescent neurons have generated unprecedented opportunities for optogenetic neuronal control, inspiring early development of optical retinal prostheses. Selectively exciting large neural populations are essential for eliciting meaningful perceptions in the brain. Here we provide the first demonstration of holographic photo-stimulation strategies for bionic vision restoration. In blind retinas, we demonstrate reliable holographically patterned optogenetic stimulation of retinal ganglion cells with millisecond temporal precision and cellular resolution. Holographic excitation strategies could enable flexible control over distributed neuronal circuits, potentially paving the way towards high-acuity vision restoration devices and additional medical and scientific neuro-photonics applications.

[1]  Aravinthan D. T. Samuel,et al.  Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans , 2011, Nature Methods.

[2]  Botond Roska,et al.  Parallel processing in retinal ganglion cells: how integration of space-time patterns of excitation and inhibition form the spiking output. , 2006, Journal of neurophysiology.

[3]  Douglas S Kim,et al.  Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration , 2008, Nature Neuroscience.

[4]  Edward S Boyden,et al.  Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[5]  A. Dizhoor,et al.  Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration , 2006, Neuron.

[6]  W. C. Hall,et al.  High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice , 2007, Proceedings of the National Academy of Sciences.

[7]  Valentina Emiliani,et al.  Three-dimensional holographic photostimulation of the dendritic arbor , 2011, Journal of neural engineering.

[8]  Luke Campagnola,et al.  Fiber-coupled light-emitting diode for localized photostimulation of neurons expressing channelrhodopsin-2 , 2008, Journal of Neuroscience Methods.

[9]  Kohji Nishida,et al.  Efficacy and Complications of Intravitreal Rituximab Injection for Treating Primary Vitreoretinal Lymphoma. , 2012, Translational vision science & technology.

[10]  Raag D. Airan,et al.  Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures , 2010, Nature Protocols.

[11]  Chethan Pandarinath,et al.  Retinal prosthetic strategy with the capacity to restore normal vision , 2012, Proceedings of the National Academy of Sciences.

[12]  A C Bird,et al.  [Macular pigment and age-related macular degeneration]. , 2001, Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft.

[13]  A. Milam,et al.  Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. , 1997, Archives of ophthalmology.

[14]  Toru Ishizuka,et al.  Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer. , 2007, Investigative ophthalmology & visual science.

[15]  N. Farah,et al.  Patterned optical activation of Channelrhodopsin II expressing retinal ganglion cells , 2007, 2007 3rd International IEEE/EMBS Conference on Neural Engineering.

[16]  Levent Onural,et al.  Digital Holographic Three-Dimensional Video Displays , 2011, Proceedings of the IEEE.

[17]  Patrick Degenaar,et al.  Multi-site optical excitation using ChR2 and micro-LED array , 2010, Journal of neural engineering.

[18]  E. Boyden,et al.  Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution , 2007, PloS one.

[19]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[20]  Herwig Baier,et al.  Remote Control of Neuronal Activity with a Light-Gated Glutamate Receptor , 2007, Neuron.

[21]  Shy Shoham,et al.  Speckle elimination using shift-averaging in high-rate holographic projection. , 2009, Optics express.

[22]  N Farah,et al.  Design and characteristics of holographic neural photo-stimulation systems , 2009, Journal of neural engineering.

[23]  Shy Shoham,et al.  Optogenetics meets optical wavefront shaping , 2010, Nature Methods.

[24]  S. Cooper,et al.  Remote Control , 2002, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[25]  R. Quian Quiroga,et al.  Unsupervised Spike Detection and Sorting with Wavelets and Superparamagnetic Clustering , 2004, Neural Computation.

[26]  Shy Shoham,et al.  Cellular Resolution Panretinal Imaging of Optogenetic Probes Using a Simple Funduscope. , 2012, Translational vision science & technology.

[27]  D Mendlovic,et al.  Optical transfer function design by use of a phase-only coherent transfer function. , 1997, Applied optics.

[28]  D H Brainard,et al.  The Psychophysics Toolbox. , 1997, Spatial vision.

[29]  Valentina Emiliani,et al.  Holographic Photolysis for Multiple Cell Stimulation in Mouse Hippocampal Slices , 2010, PloS one.

[30]  Rafael Yuste,et al.  Two-photon optogenetics of dendritic spines and neural circuits in 3D , 2012, Nature Methods.

[31]  Konrad Lehmann,et al.  Visual Function in Mice with Photoreceptor Degeneration and Transgenic Expression of Channelrhodopsin 2 in Ganglion Cells , 2010, The Journal of Neuroscience.

[32]  Hongxin Huang,et al.  Stabilized high-accuracy correction of ocular aberrations with liquid crystal on silicon spatial light modulator in adaptive optics retinal imaging system. , 2011, Optics express.

[33]  Giancarlo Ruocco,et al.  Computer generation of optimal holograms for optical trap arrays. , 2007, Optics express.

[34]  Mark A. A. Neil,et al.  Programmable binary phase-only optical device based on ferroelectric liquid crystal SLM , 1992 .

[35]  Xue Han,et al.  Prosthetic systems for therapeutic optical activation and silencing of genetically targeted neurons , 2008, SPIE BiOS.

[36]  F. Werblin,et al.  Differential Targeting of Optical Neuromodulators to Ganglion Cell Soma and Dendrites Allows Dynamic Control of Center-Surround Antagonism , 2011, Neuron.

[37]  Valentina Emiliani,et al.  Reshaping the optical dimension in optogenetics , 2012, Current Opinion in Neurobiology.

[38]  Shy Shoham,et al.  Reduction of two-photon holographic speckle using shift-averaging. , 2011, Optics express.

[39]  Sharad Ramanathan,et al.  Optical interrogation of neural circuits in Caenorhabditis elegans , 2009, Nature Methods.

[40]  Feng Zhang,et al.  An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology , 2007, Journal of neural engineering.

[41]  Valentina Emiliani,et al.  Patterned two-photon illumination by spatiotemporal shaping of ultrashort pulses. , 2008, Optics express.

[42]  Shy Shoham,et al.  Rapid neurotransmitter uncaging in spatially defined patterns , 2005, Nature Methods.

[43]  E. Isacoff,et al.  Scanless two-photon excitation of channelrhodopsin-2 , 2010, Nature Methods.

[44]  Brendon O. Watson,et al.  SLM Microscopy: Scanless Two-Photon Imaging and Photostimulation with Spatial Light Modulators , 2008, Frontiers in neural circuits.

[45]  Christoph Lutz,et al.  Holographic photolysis of caged neurotransmitters , 2008, Nature Methods.

[46]  Stephen A. Baccus,et al.  Image Processing for a High-Resolution Optoelectronic Retinal Prosthesis , 2007, IEEE Transactions on Biomedical Engineering.

[47]  Michel Paques,et al.  Panretinal, high-resolution color photography of the mouse fundus. , 2007, Investigative ophthalmology & visual science.