Studying a Light Sensor with Light: Multiphoton Imaging in the Retina

Two-photon imaging of light stimulus-evoked neuronal activity has been used to study all neuron classes in the vertebrate retina, from the photoreceptors to the retinal ganglion cells. Clearly, the ability to study retinal circuits down to the level of single synapses or zoomed out at the level of complete populations of neurons, has been a major asset in our understanding of this beautiful circuit. In this chapter, we discuss the possibilities and pitfalls of using an all-optical approach in this highly light-sensitive part of the brain.

[1]  R. Hindges,et al.  Neural Mechanisms Generating Orientation Selectivity in the Retina , 2016, Current Biology.

[2]  Thomas Euler,et al.  Chromatic Coding from Cone-type Unselective Circuits in the Mouse Retina , 2013, Neuron.

[3]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[4]  Marla B Feller,et al.  Two-photon targeted recording of GFP-expressing neurons for light responses and live-cell imaging in the mouse retina , 2010, Nature Protocols.

[5]  Alon Poleg-Polsky,et al.  Retinal Circuitry Balances Contrast Tuning of Excitation and Inhibition to Enable Reliable Computation of Direction Selectivity , 2016, The Journal of Neuroscience.

[6]  Tobias Breuninger,et al.  Eyecup scope—optical recordings of light stimulus-evoked fluorescence signals in the retina , 2009, Pflügers Archiv - European Journal of Physiology.

[7]  Kevin L. Briggman,et al.  Wiring specificity in the direction-selectivity circuit of the retina , 2011, Nature.

[8]  B. Boycott,et al.  The morphological types of ganglion cells of the domestic cat's retina , 1974, The Journal of physiology.

[9]  M. Meister,et al.  A neuronal circuit for colour vision based on rod–cone opponency , 2016, Nature.

[10]  F S Werblin,et al.  Transmission along and between rods in the tiger salamander retina. , 1978, The Journal of physiology.

[11]  K. Fujita.  [Two-photon laser scanning fluorescence microscopy]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[12]  G. Ruxton,et al.  Metabolic rate and body size are linked with perception of temporal information☆ , 2013, Animal Behaviour.

[13]  Yongxin Zhao,et al.  An Expanded Palette of Genetically Encoded Ca2+ Indicators , 2011, Science.

[14]  Vladimir J. Kefalov,et al.  The Cone-specific visual cycle , 2011, Progress in Retinal and Eye Research.

[15]  Masahito Yamagata,et al.  Two Pairs of ON and OFF Retinal Ganglion Cells Are Defined by Intersectional Patterns of Transcription Factor Expression. , 2016, Cell reports.

[16]  G. H. Jacobs,et al.  Retinal receptors in rodents maximally sensitive to ultraviolet light , 1991, Nature.

[17]  G. Aguirre,et al.  Unique topographic separation of two spectral classes of cones in the mouse retina , 1992, The Journal of comparative neurology.

[18]  Nicholas Oesch,et al.  Direction-Selective Dendritic Action Potentials in Rabbit Retina , 2005, Neuron.

[19]  J. Diamond,et al.  Retinal Parallel Processors: More than 100 Independent Microcircuits Operate within a Single Interneuron , 2010, Neuron.

[20]  David Williams,et al.  Imaging Light Responses of Foveal Ganglion Cells in the Living Macaque Eye , 2014, The Journal of Neuroscience.

[21]  P. Detwiler,et al.  Directionally selective calcium signals in dendrites of starburst amacrine cells , 2002, Nature.

[22]  Maxime J. Y. Zimmermann,et al.  Zebrafish differentially process colour across visual space to match natural scenes , 2017, bioRxiv.

[23]  R. Campbell,et al.  Genetically Encoded Glutamate Indicators with Altered Color and Topology. , 2018, ACS chemical biology.

[24]  Wei Wei,et al.  Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity , 2016, eLife.

[25]  F. Esposti,et al.  Spikes in Retinal Bipolar Cells Phase-Lock to Visual Stimuli with Millisecond Precision , 2011, Current Biology.

[26]  L. Peichl.  Diversity of mammalian photoreceptor properties: adaptations to habitat and lifestyle? , 2005, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[27]  P. Detwiler,et al.  Optical recording of light-evoked calcium signals in the functionally intact retina. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[29]  Jasper Akerboom,et al.  Optimization of a GCaMP Calcium Indicator for Neural Activity Imaging , 2012, The Journal of Neuroscience.

[30]  J. Marvin,et al.  Two-Photon Imaging of Nonlinear Glutamate Release Dynamics at Bipolar Cell Synapses in the Mouse Retina , 2013, The Journal of Neuroscience.

[31]  L. B. Arey.  The movements in the visual cells and retinal pigment of the lower vertebrates , 1916 .

[32]  Thomas Euler,et al.  Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina , 2015, Journal of visualized experiments : JoVE.

[33]  Thomas Euler,et al.  Calcium dynamics change in degenerating cone photoreceptors. , 2016, Human molecular genetics.

[34]  P. Detwiler,et al.  Longitudinal spread of second messenger signals in isolated rod outer segments of lizards , 1999, The Journal of physiology.

[35]  Leon Lagnado,et al.  A genetically-encoded reporter of synaptic activity in vivo , 2009, Nature Methods.

[36]  Tobias Breuninger,et al.  Chromatic Bipolar Cell Pathways in the Mouse Retina , 2011, The Journal of Neuroscience.

[37]  P. Lewis.  A theoretical interpretation of spectral sensitivity curves at long wavelengths , 1955, The Journal of physiology.

[38]  F. Esposti,et al.  Olfactory Stimulation Selectively Modulates the OFF Pathway in the Retina of Zebrafish , 2013, Neuron.

[39]  F. Esposti,et al.  A Synaptic Mechanism for Temporal Filtering of Visual Signals , 2014, PLoS biology.

[40]  Alon Poleg-Polsky,et al.  Species-specific wiring for direction selectivity in the mammalian retina , 2016, Nature.

[41]  Alexander Borst,et al.  A FRET-based calcium biosensor with fast signal kinetics and high fluorescence change. , 2006, Biophysical journal.

[42]  Adam Bleckert,et al.  Visual Space Is Represented by Nonmatching Topographies of Distinct Mouse Retinal Ganglion Cell Types , 2014, Current Biology.

[43]  Thomas Cremer,et al.  Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution , 2009, Cell.

[44]  Local signal processing in mouse horizontal cell dendrites , 2017 .

[45]  L. Lagnado,et al.  Synaptic mechanisms of adaptation and sensitization in the retina , 2013, Nature Neuroscience.

[46]  Hongkui Zeng,et al.  A Cre-Dependent GCaMP3 Reporter Mouse for Neuronal Imaging In Vivo , 2012, The Journal of Neuroscience.

[47]  Thomas Euler,et al.  GABA\(_A\) Receptors Containing the \(\alpha\)2 Subunit Are Critical for Direction-Selective Inhibition in the Retina , 2012 .

[48]  Bin Lin,et al.  Populations of wide‐field amacrine cells in the mouse retina , 2006, The Journal of comparative neurology.

[49]  P. Detwiler,et al.  A Dendrite-Autonomous Mechanism for Direction Selectivity in Retinal Starburst Amacrine Cells , 2007, PLoS biology.

[50]  L. Vandenberghe,et al.  Novel adeno-associated viral vectors for retinal gene therapy , 2011, Gene Therapy.

[51]  B. Borghuis,et al.  Kainate Receptors Mediate Signaling in Both Transient and Sustained OFF Bipolar Cell Pathways in Mouse Retina , 2014, The Journal of Neuroscience.

[52]  Krzysztof Palczewski,et al.  Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye , 2014, Nature Medicine.

[53]  K. Svoboda,et al.  Photon Upmanship: Why Multiphoton Imaging Is More than a Gimmick , 1997, Neuron.

[54]  L. Peichl,et al.  Morphological types of horizontal cell in rodent retinae: A comparison of rat, mouse, gerbil, and guinea pig , 1994, Visual Neuroscience.

[55]  Matthias Bethge,et al.  The functional diversity of retinal ganglion cells in the mouse , 2015, Nature.

[56]  Benjamin Sivyer,et al.  Direction selectivity in the retina: symmetry and asymmetry in structure and function , 2012, Nature Reviews Neuroscience.

[57]  Hongkui Zeng,et al.  Local processing of visual information in neurites of VGluT3-expressing amacrine cells , 2017, bioRxiv.

[58]  L. Lavis.  Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines. , 2017, Annual review of biochemistry.

[59]  Mark T. Harnett,et al.  An optimized fluorescent probe for visualizing glutamate neurotransmission , 2013, Nature Methods.

[60]  Yi Zhang,et al.  Segregated Glycine-Glutamate Co-transmission from vGluT3 Amacrine Cells to Contrast-Suppressed and Contrast-Enhanced Retinal Circuits , 2016, Neuron.

[61]  M. Bethge,et al.  Inhibition decorrelates visual feature representations in the inner retina , 2017, Nature.

[62]  K. Yau,et al.  How vision begins: An odyssey , 2008, Proceedings of the National Academy of Sciences.

[63]  Jonathan B. Demb,et al.  Spectral and Temporal Sensitivity of Cone-Mediated Responses in Mouse Retinal Ganglion Cells , 2011, The Journal of Neuroscience.

[64]  John A Gemmer,et al.  A retinal code for motion along the gravitational and body axes , 2017, Nature.

[65]  David C. Sterratt,et al.  Standard Anatomical and Visual Space for the Mouse Retina: Computational Reconstruction and Transformation of Flattened Retinae with the Retistruct Package , 2013, PLoS Comput. Biol..

[66]  Hongkui Zeng,et al.  An R-CaMP1.07 reporter mouse for cell-type-specific expression of a sensitive red fluorescent calcium indicator , 2017, PloS one.

[67]  Deniz Dalkara,et al.  In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous , 2013, Science Translational Medicine.

[68]  Thomas Euler,et al.  Two-Photon Imaging Reveals Somatodendritic Chloride Gradient in Retinal ON-Type Bipolar Cells Expressing the Biosensor Clomeleon , 2006, Neuron.

[69]  Botond Roska,et al.  The First Stage of Cardinal Direction Selectivity Is Localized to the Dendrites of Retinal Ganglion Cells , 2013, Neuron.

[70]  Gerald H Jacobs,et al.  The evolution of vertebrate color vision. , 2012, Advances in experimental medicine and biology.

[71]  Bart G Borghuis,et al.  Excitatory Synaptic Inputs to Mouse On-Off Direction-Selective Retinal Ganglion Cells Lack Direction Tuning , 2014, The Journal of Neuroscience.

[72]  M. Bethge,et al.  Spikes in Mammalian Bipolar Cells Support Temporal Layering of the Inner Retina , 2013, Current Biology.

[73]  T. Lamb,et al.  Photoreceptor spectral sensitivities: Common shape in the long-wavelength region , 1995, Vision Research.

[74]  N. Vesselkin,et al.  The centrifugal visual system of vertebrates: A comparative analysis of its functional anatomical organization , 2006, Brain Research Reviews.

[75]  L. Lagnado,et al.  Encoding of Luminance and Contrast by Linear and Nonlinear Synapses in the Retina , 2012, Neuron.

[76]  J. Sanes,et al.  The most numerous ganglion cell type of the mouse retina is a selective feature detector , 2012, Proceedings of the National Academy of Sciences.

[77]  Eric A Newman,et al.  An eyecup preparation for the rat and mouse , 1999, Journal of Neuroscience Methods.

[78]  Michael Z. Lin,et al.  Genetically encoded indicators of neuronal activity , 2016, Nature Neuroscience.

[79]  B. Sagdullaev,et al.  Optimized protocol for retinal wholemount preparation for imaging and immunohistochemistry. , 2013, Journal of visualized experiments : JoVE.

[80]  Thomas Euler,et al.  Bulk electroporation and population calcium imaging in the adult mammalian retina. , 2011, Journal of neurophysiology.

[81]  R. Hindges,et al.  A crystal-clear zebrafish for in vivo imaging , 2016, Scientific Reports.

[82]  Thomas Euler,et al.  A Tale of Two Retinal Domains: Near-Optimal Sampling of Achromatic Contrasts in Natural Scenes through Asymmetric Photoreceptor Distribution , 2013, Neuron.

[83]  L. Lagnado,et al.  Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina , 2016, Neuron.

[84]  Paul R. Martin,et al.  Comparison of photoreceptor spatial density and ganglion cell morphology in the retina of human, macaque monkey, cat, and the marmoset Callithrix jacchus , 1996, The Journal of comparative neurology.

[85]  Thomas Euler,et al.  Differential Regulation of Cone Calcium Signals by Different Horizontal Cell Feedback Mechanisms in the Mouse Retina , 2014, The Journal of Neuroscience.

[86]  James J. Chambers,et al.  A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors , 2011, PLoS biology.

[87]  Thomas Euler,et al.  Toxicity assessment of intravitreal triamcinolone and bevacizumab in a retinal explant mouse model using two-photon microscopy. , 2009, Investigative ophthalmology & visual science.

[88]  Thomas Euler,et al.  Light-Driven Calcium Signals in Mouse Cone Photoreceptors , 2012, The Journal of Neuroscience.

[89]  Edward N. Pugh,et al.  From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG , 2004, Vision Research.

[90]  David Fitzpatrick,et al.  Stability, affinity and chromatic variants of the glutamate sensor iGluSnFR , 2018, Nature Methods.

[91]  M. Kano,et al.  A highly sensitive fluorescent indicator dye for calcium imaging of neural activity in vitro and in vivo , 2014, The European journal of neuroscience.

[92]  Takeharu Nagai,et al.  Functional Fluorescent Ca2+ Indicator Proteins in Transgenic Mice under TET Control , 2004, PLoS biology.

[93]  X. Breakefield,et al.  Viral vectors for gene delivery to the nervous system , 2003, Nature Reviews Neuroscience.

[94]  Maria Goeppert-Mayer.  Über Elementarakte mit zwei Quantensprüngen , 1931 .