A Positive Feedback Synapse from Retinal Horizontal Cells to Cone Photoreceptors

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca2+ and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca2+, whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement.

[1]  S. Barnes,et al.  Carbenoxolone inhibition of voltage-gated Ca channels and synaptic transmission in the retina. , 2004, Journal of neurophysiology.

[2]  S. Naghshineh,et al.  Action of glutamate and aspartate analogues on rod horizontal and bipolar cells , 1981, Nature.

[3]  H. Wässle,et al.  Glutamate Responses of Bipolar Cells in a Slice Preparation of the Rat Retina , 1996, The Journal of Neuroscience.

[4]  Norbert Babai,et al.  Horizontal cell feedback regulates calcium currents and intracellular calcium levels in rod photoreceptors of salamander and mouse retina , 2009, The Journal of physiology.

[5]  C. M. Davenport,et al.  Effects of pH Buffering on Horizontal and Ganglion Cell Light Responses in Primate Retina: Evidence for the Proton Hypothesis of Surround Formation , 2008, The Journal of Neuroscience.

[6]  R. Weiler,et al.  Selective synaptic distribution of AMPA and kainate receptor subunits in the outer plexiform layer of the carp retina , 2001, The Journal of comparative neurology.

[7]  Norbert Babai,et al.  Vesicle pool size at the salamander cone ribbon synapse. , 2010, Journal of neurophysiology.

[8]  R. Hawkins,et al.  Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. , 1998, Progress in brain research.

[9]  K. Rábl,et al.  Activation of glutamate transporters in rods inhibits presynaptic calcium currents , 2003, Visual Neuroscience.

[10]  Peter Sterling,et al.  Encoding Light Intensity by the Cone Photoreceptor Synapse , 2005, Neuron.

[11]  M Kamermans,et al.  Hemichannel-Mediated Inhibition in the Outer Retina , 2001, Science.

[12]  R. S. St Jules,et al.  L‐type calcium channels in the photoreceptor ribbon synapse: Localization and role in plasticity , 1999, The Journal of comparative neurology.

[13]  H. Wässle,et al.  Modulation of the intracellular calcium concentration in photoreceptor terminals by a presynaptic metabotropic glutamate receptor. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Dacheux,et al.  Rabbit cone bipolar cells: Correlation of their morphologies with whole-cell recordings , 2001, Visual Neuroscience.

[15]  W. Thoreson,et al.  Feedback effects of horizontal cell membrane potential on cone calcium currents studied with simultaneous recordings. , 2006, Journal of neurophysiology.

[16]  C. Remé,et al.  Lipid mediators in the rat retina: light exposure and trauma elicit leukotriene B4 release in vitro. , 1995, Current eye research.

[17]  B Ehinger,et al.  The interplexiform cell system - I. Synapses of the dopaminergic neurons of the goldfish retina , 1978, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[18]  Richard H. Kramer,et al.  Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide , 1997, Nature.

[19]  Hans H. Jung,et al.  Light-evoked arachidonic acid release in the retina: illuminance/duration dependence and the effects of quinacrine, mellitin and lithium , 1994, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  Paul Witkovsky,et al.  Chapter 10 Functional roles of dopamine in the vertebrate retina , 1991 .

[21]  J. Dowling,et al.  Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer. , 1985, Journal of neurophysiology.

[22]  William H Baldridge,et al.  Proton-Mediated Feedback Inhibition of Presynaptic Calcium Channels at the Cone Photoreceptor Synapse , 2005, The Journal of Neuroscience.

[23]  A. Kaneko,et al.  L-glutamate-induced responses and cGMP-activated channels in three subtypes of retinal bipolar cells dissociated from the cat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  S. Massey,et al.  Localization of nitric oxide synthase, NADPH diaphorase and soluble guanylyl cyclase in adult rabbit retina , 1998, Visual Neuroscience.

[25]  K. Nakatani,et al.  Effects of GABA on neuronal activities in the distal retina of the carp. , 1978, Sensory processes.

[26]  Peter Sterling,et al.  Synaptic Ca2+ in Darkness Is Lower in Rods than Cones, Causing Slower Tonic Release of Vesicles , 2007, The Journal of Neuroscience.

[27]  G. Ellis‐Davies,et al.  Caged compounds: photorelease technology for control of cellular chemistry and physiology , 2007, Nature Methods.

[28]  Ji-Jie Pang,et al.  How do tonic glutamatergic synapses evade receptor desensitization? , 2008, The Journal of physiology.

[29]  W. G. Owen,et al.  Spatial organization of the bipolar cell's receptive field in the retina of the tiger salamander. , 1990, The Journal of physiology.

[30]  R. G. Smith,et al.  Simulation of an anatomically defined local circuit: The cone-horizontal cell network in cat retina , 1995, Visual Neuroscience.

[31]  F. Werblin,et al.  Characterization of the glutamate transporter in retinal cones of the tiger salamander , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  S. Yasui,et al.  Ca2+ regulation by the Na+-Ca2+ exchanger in retinal horizontal cells depolarized by l-glutamate , 1998, Neuroscience Research.

[33]  H. Spekreijse,et al.  Horizontal cells feed back to cones by shifting the cone calcium-current activation range , 1996, Vision Research.

[34]  D. Baylor,et al.  Receptive fields of cones in the retina of the turtle , 1971, The Journal of physiology.

[35]  J. Dowling,et al.  Organization of the retina of the mudpuppy, Necturus maculosus. II. Intracellular recording. , 1969, Journal of neurophysiology.

[36]  H. Lecar,et al.  Glutamate-gated chloride channel with glutamate-transporter-like properties in cone photoreceptors of the tiger salamander. , 1995, Journal of neurophysiology.

[37]  M. Yamada,et al.  A Metabotropic Glutamate Receptor Regulates Transmitter Release from Cone Presynaptic Terminals in Carp Retinal Slices , 2002, The Journal of general physiology.

[38]  E. Raviola,et al.  Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. A freeze-fracture study in monkeys and rabbits , 1975, The Journal of cell biology.

[39]  Peter J. S. Smith,et al.  Modulation of Extracellular Proton Fluxes from Retinal Horizontal Cells of the Catfish by Depolarization and Glutamate , 2007, The Journal of general physiology.

[40]  A. Kaneko,et al.  L-glutamate-induced depolarization in solitary photoreceptors: a process that may contribute to the interaction between photoreceptors in situ. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[41]  P. Barabas,et al.  Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors , 2008, The Journal of physiology.

[42]  W. Eldred,et al.  Functional localization of the nitric oxide/cGMP pathway in the salamander retina , 2009, Visual Neuroscience.

[43]  S. Wu,et al.  Feedback connections and operation of the outer plexiform layer of the retina , 1992, Current Opinion in Neurobiology.

[44]  R A Normann,et al.  The effects of GABA and related drugs on horizontal cells in the isolated turtle retina , 1990, Visual Neuroscience.

[45]  Akimichi Kaneko,et al.  pH Changes in the Invaginating Synaptic Cleft Mediate Feedback from Horizontal Cells to Cone Photoreceptors by Modulating Ca2+ Channels , 2003, The Journal of general physiology.

[46]  R. Zucker,et al.  Magnesium binding to DM-nitrophen and its effect on the photorelease of calcium. , 1999, Biophysical journal.

[47]  A. L. Byzov,et al.  Electrical feedback mechanism in the processing of signals in the outer plexiform layer of the retina , 1986, Vision Research.

[48]  D. Hubel,et al.  Receptive fields of single neurones in the cat's striate cortex , 1959, The Journal of physiology.

[49]  Maarten Kamermans,et al.  Lateral Gain Control in the Outer Retina Leads to Potentiation of Center Responses of Retinal Neurons , 2009, The Journal of Neuroscience.

[50]  B. Christensen,et al.  A voltage-clamp study of isolated stingray horizontal cell non-NMDA excitatory amino acid receptors. , 1989, Journal of neurophysiology.

[51]  E. A. Schwartz,et al.  Transport-mediated synapses in the retina. , 2002, Physiological reviews.

[52]  P. de la Villa,et al.  Calcium-permeable glutamate receptors in horizontal cells of the mammalian retina , 2001, Visual Neuroscience.

[53]  David J. Calkins,et al.  Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina , 2005, Visual Neuroscience.

[54]  J. Dowling,et al.  Roles of aspartate and glutamate in synaptic transmission in rabbit retina. II. Inner plexiform layer. , 1985, Journal of neurophysiology.

[55]  A. Kaneko,et al.  GABA-mediated component in the feedback response of turtle retinal cones , 2005, Visual Neuroscience.

[56]  V. Vellani,et al.  Modulation of the synaptic Ca2+ current in salamander photoreceptors by polyunsaturated fatty acids and retinoids , 2000, The Journal of physiology.

[57]  S. Yazulla.  Endocannabinoids in the retina: From marijuana to neuroprotection , 2008, Progress in Retinal and Eye Research.

[58]  Helga Kolb,et al.  Outer Plexiform Layer , 2007 .

[59]  W. Thoreson,et al.  Feedback from Horizontal Cells to Rod Photoreceptors in Vertebrate Retina , 2008, The Journal of Neuroscience.

[60]  P. England,et al.  A subtype-selective, use-dependent inhibitor of native AMPA receptors. , 2007, Journal of the American Chemical Society.

[61]  J. Dowling,et al.  Carp horizontal cells in culture respond selectively to L-glutamate and its agonists. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[62]  E. Hartveit.  Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation. , 1996, Journal of neurophysiology.

[63]  K. Koch,et al.  Photoreceptor specific guanylate cyclases in vertebrate phototransduction , 2004, Molecular and Cellular Biochemistry.

[64]  D. A. Burkhardt,et al.  Effects of synaptic blocking agents on the depolarizing responses of turtle cones evoked by surround illumination , 1990, Visual Neuroscience.

[65]  B. Hille,et al.  Ionic channels of the inner segment of tiger salamander cone photoreceptors , 1989, The Journal of general physiology.

[66]  Masahiro Yamada,et al.  Depolarization of isolated horizontal cells of fish acidifies their immediate surrounding by activating V‐ATPase , 2007, The Journal of physiology.

[67]  E. A. Schwartz,et al.  A cGMP-gated current can control exocytosis at cone synapses , 1994, Neuron.

[68]  W. Eldred,et al.  Subcellular localization of neuronal nitric oxide synthase in turtle retina: Electron immunocytochemistry , 2001, Visual Neuroscience.

[69]  A. Hendrickson,et al.  Distribution of the glycine transporter glyt-1 in mammalian and nonmammalian retinae , 1999, Visual Neuroscience.

[70]  J. Rabin.  The Retina: An Approachable Part of the Brain , 2013 .

[71]  J. Sahel,et al.  Glycine receptors in a population of adult mammalian cones , 2006, The Journal of physiology.

[72]  H. Wässle,et al.  Immunocytochemical labelling of horizontal cells in mammalian retina using antibodies against calcium-binding proteins , 1987, Neuroscience Letters.

[73]  P. Sterling,et al.  Streamlined Synaptic Vesicle Cycle in Cone Photoreceptor Terminals , 2004, Neuron.

[74]  E. Raviola,et al.  Gap junctions between photoreceptor cells in the vertebrate retina. , 1973, Proceedings of the National Academy of Sciences of the United States of America.