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Evidence for functional GABAA but not GABAC receptors in mouse cone photoreceptors

Published online by Cambridge University Press:  29 April 2019

Sercan Deniz
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Translational Medicine and Neurogenetics, F-67404, Illkirch, France Centre National de la Recherche Scientifique, UMR7104, F-67404, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U1258, F-67404, Illkirch, France Université de Strasbourg, F-67404, Illkirch, France
Eric Wersinger
Affiliation:
UMR 1107 INSERM/UCA NEURO-DOL, Université Clermont Auvergne, F-63001 Clermont-Ferrand, France
Serge Picaud
Affiliation:
Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France
Michel J. Roux*
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Translational Medicine and Neurogenetics, F-67404, Illkirch, France Centre National de la Recherche Scientifique, UMR7104, F-67404, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U1258, F-67404, Illkirch, France Université de Strasbourg, F-67404, Illkirch, France
*
*Address correspondence to: Michel J. Roux, Email: mjroux@igbmc.fr

Abstract

At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic mechanisms through which these modulations occur are still debated. The initial hypothesis of a GABAergic feedback from HCs to cones has been challenged by pharmacological inconsistencies. Surround antagonism has been demonstrated to occur via a modulation of cone calcium channels through ephaptic signaling and pH changes in the synaptic cleft. GABAergic transmission between HCs and cones has been reported in some lower vertebrates, like the turtle and tiger salamander. In these reports, it was revealed that GABA is released from HCs through reverse transport and target GABA receptors are located at the cone terminals. In mammalian retinas, there is growing evidence that HCs can release GABA through conventional vesicular transmission, acting both on autaptic GABA receptors and on receptors expressed at the dendritic tips of the bipolar cells. The presence of GABA receptors on mammalian cone terminals remains equivocal. Here, we looked specifically for functional GABA receptors in mouse photoreceptors by recording in the whole-cell or amphotericin/gramicidin-perforated patch clamp configurations. Cones could be differentiated from rods through morphological criteria. Local GABA applications evoked a Cl current in cones but not in rods. It was blocked by the GABAA receptor antagonist bicuculline methiodide and unaffected by the GABAC receptor antagonist TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid]. The voltage dependency of the current amplitude was as expected from a direct action of GABA on cone pedicles but not from an indirect modulation of cone currents following the activation of the GABA receptors of HCs. This supports a direct role of GABA released from HCs in the control of cone activity in the mouse retina.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2019 

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Footnotes

Present address: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

References

Agardh, E., Bruun, A., Ehinger, B. & Storm-Mathisen, J. (1986). GABA immunoreactivity in the retina. Investigative Ophthalmology & Visual Science 27, 674678.Google ScholarPubMed
Babai, N., Kanevsky, N., Dascal, N., Rozanski, G.J., Singh, D.P., Fatma, N. & Thoreson, W.B. (2010). Anion-sensitive regions of L-type CaV1.2 calcium channels expressed in HEK293 cells. PLoS One 5, e8602.CrossRefGoogle ScholarPubMed
Barnes, S. & Bui, Q. (1991). Modulation of calcium-activated chloride current via pH-induced changes of calcium channel properties in cone photoreceptors. Journal of Neuroscience 11, 40154023.CrossRefGoogle ScholarPubMed
Barnes, S. & Hille, B. (1989). Ionic channels of the inner segment of tiger salamander cone photoreceptors. The Journal of General Physiology 94, 719743.CrossRefGoogle ScholarPubMed
Baylor, D.A., Fuortes, M.G. & O’Bryan, P.M. (1971). Receptive fields of cones in the retina of the turtle. Journal of Physiology (London) 214, 265294.CrossRefGoogle ScholarPubMed
Brecha, N.C., Sternini, C. & Humphrey, M.F. (1991). Cellular distribution of L-glutamate decarboxylase (GAD) and gamma-aminobutyric acidA (GABAA) receptor mRNAs in the retina. Cellular and Molecular Neurobiology 11, 497509.CrossRefGoogle ScholarPubMed
Busskamp, V., Duebel, J., Balya, D., Fradot, M., Viney, T.J., Siegert, S., Groner, A.C., Cabuy, E., Forster, V., Seeliger, M., Biel, M., Humphries, P., Paques, M., Mohand-Said, S., Trono, D., Deisseroth, K., Sahel, J.A., Picaud, S. & Roska, B. (2010). Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329, 413417.CrossRefGoogle ScholarPubMed
Cangiano, L., Asteriti, S., Cervetto, L. & Gargini, C. (2012). The photovoltage of rods and cones in the dark-adapted mouse retina. Journal of Physiology (London) 590, 38413855.CrossRefGoogle ScholarPubMed
Chapot, C.A., Euler, T. & Schubert, T. (2017). How do horizontal cells ‘talk’ to cone photoreceptors? Different levels of complexity at the cone-horizontal cell synapse. Journal of Physiology (London) 595, 54955506.CrossRefGoogle ScholarPubMed
Chavas, J., Forero, M.E., Collin, T., Llano, I. & Marty, A. (2004). Osmotic tension as a possible link between GABAA receptor activation and intracellular calcium elevation. Neuron 44, 701713.CrossRefGoogle Scholar
Cueva, J.G., Haverkamp, S., Reimer, R.J., Edwards, R., Wässle, H. & Brecha, N.C. (2002). Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells. Journal of Comparative Neurology 445, 227237.CrossRefGoogle ScholarPubMed
Davenport, C.M., Detwiler, P.B. & Dacey, D.M. (2008). Effects of pH buffering on horizontal and ganglion cell light responses in primate retina: Evidence for the proton hypothesis of surround formation. Journal of Neuroscience 28, 456464.CrossRefGoogle ScholarPubMed
Deniz, S., Wersinger, E., Schwab, Y., Mura, C., Erdelyi, F., Szabó, G., Rendon, A., Sahel, J.-A., Picaud, S. & Roux, M.J. (2011). Mammalian retinal horizontal cells are unconventional GABAergic neurons. Journal of Neurochemistry 116, 350362.CrossRefGoogle ScholarPubMed
Ebihara, S., Marks, T., Hudson, D.J. & Menaker, M. (1986). Genetic control of melatonin synthesis in the pineal gland of the mouse. Science 231, 491493.CrossRefGoogle ScholarPubMed
Fahrenfort, I., Steijaert, M., Sjoerdsma, T., Vickers, E., Ripps, H., van Asselt, J., Endeman, D., Klooster, J., Numan, R., ten Eikelder, H., von Gersdorff, H. & Kamermans, M. (2009). Hemichannel-mediated and pH-based feedback from horizontal cells to cones in the vertebrate retina. PLoS One 4, e6090.CrossRefGoogle ScholarPubMed
Fletcher, E.L. & Kalloniatis, M. (1997). Localisation of amino acid neurotransmitters during postnatal development of the rat retina. Journal of Comparative Neurology 380, 449471.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Greferath, U., Grünert, U., Fritschy, J.M., Stephenson, A., Möhler, H. & Wässle, H. (1995). GABAA receptor subunits have differential distributions in the rat retina: In situ hybridization and immunohistochemistry. Journal of Comparative Neurology 353, 553571.CrossRefGoogle ScholarPubMed
Greferath, U., Grünert, U., Müller, F. & Wässle, H. (1994). Localization of GABAA receptors in the rabbit retina. Cell and Tissue Research 276, 295307.Google ScholarPubMed
Greferath, U., Müller, F., Wässle, H., Shivers, B. & Seeburg, P. (1993). Localization of GABAA receptors in the rat retina. Visual Neuroscience 10, 551561.CrossRefGoogle ScholarPubMed
Grigorenko, E.V. & Yeh, H.H. (1994). Expression profiling of GABAA receptor beta-subunits in the rat retina. Visual Neuroscience 11, 379387.CrossRefGoogle ScholarPubMed
Guo, C., Hirano, A.A., Stella, S.L. Jr., Bitzer, M. & Brecha, N.C. (2010). Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD65, and the GABA vesicular transporter. Journal of Comparative Neurology 518, 16471669.CrossRefGoogle Scholar
Haverkamp, S., Grünert, U. & Wässle, H. (2000). The cone pedicle, a complex synapse in the retina. Neuron 27, 8595.CrossRefGoogle ScholarPubMed
Hirano, A.A., Brandstätter, J.H. & Brecha, N.C. (2005). Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina. Journal of Comparative Neurology 488, 7081.CrossRefGoogle ScholarPubMed
Hirano, A.A., Liu, X., Boulter, J., Grove, J., Pérez de Sevilla Müller, L., Barnes, S. & Brecha, N.C. (2016). Targeted deletion of vesicular GABA transporter from retinal horizontal cells eliminates feedback modulation of photoreceptor calcium channels. eNeuro. 3(1), 148160, doi: 10.1523/ENEURO.0148-15.2016.CrossRefGoogle ScholarPubMed
Hirasawa, H. & Kaneko, A. (2003). pH changes in the invaginating synaptic cleft mediate feedback from horizontal cells to cone photoreceptors by modulating Ca2+ channels. The Journal of General Physiology 122, 657671.CrossRefGoogle ScholarPubMed
Jackman, S.L., Babai, N., Chambers, J.J., Thoreson, W.B. & Kramer, R.H. (2011). A positive feedback synapse from retinal horizontal cells to cone photoreceptors. PLoS Biology 9, e1001057.CrossRefGoogle ScholarPubMed
Jellali, A., Stussi-Garaud, C., Gasnier, B., Rendon, A., Sahel, J.-A., Dreyfus, H. & Picaud, S. (2002). Cellular localization of the vesicular inhibitory amino acid transporter in the mouse and human retina. Journal of Comparative Neurology 449, 7687.CrossRefGoogle ScholarPubMed
Jeon, C-J., Strettoi, E. & Masland, R.H. (1998). The major cell populations of the mouse retina. Journal of Neuroscience 18, 89368946.CrossRefGoogle ScholarPubMed
Jilge, B. (1991). The rabbit: A diurnal or a nocturnal animal? Journal of Experimental Animal Science 34, 170183.Google ScholarPubMed
Kamermans, M. & Fahrenfort, I. (2004). Ephaptic interactions within a chemical synapse: Hemichannel-mediated ephaptic inhibition in the retina. Current Opinion in Neurobiology 14, 531541.CrossRefGoogle ScholarPubMed
Kamermans, M., Fahrenfort, I., Schultz, K., Janssen-Bienhold, U., Sjoerdsma, T. & Weiler, R. (2001). Hemichannel-mediated inhibition in the outer retina. Science 292, 11781180.CrossRefGoogle ScholarPubMed
Kaneko, A. & Tachibana, M. (1986). Effects of gamma-aminobutyric acid on isolated cone photoreceptors of the turtle retina. Journal of Physiology (London) 373, 443461.CrossRefGoogle ScholarPubMed
Kemmler, R., Schultz, K., Dedek, K., Euler, T. & Schubert, T. (2014). Differential regulation of cone calcium signals by different horizontal cell feedback mechanisms in the mouse retina. Journal of Neuroscience 34, 1182611843.CrossRefGoogle ScholarPubMed
Klaassen, L.J., Sun, Z., Steijaert, M.N., Bolte, P., Fahrenfort, I., Sjoerdsma, T., Klooster, J., Claassen, Y., Shields, C.R., Ten Eikelder, H.M.M., Janssen-Bienhold, U., Zoidl, G., McMahon, D.G. & Kamermans, M. (2011). Synaptic transmission from horizontal cells to cones is impaired by loss of connexin hemichannels. PLoS Biology 9, e1001107.CrossRefGoogle ScholarPubMed
Kraaij, D.A., Spekreijse, H. & Kamermans, M. (2000). The nature of surround-induced depolarizing responses in goldfish cones. The Journal of General Physiology 115, 316.CrossRefGoogle ScholarPubMed
Lee, H. & Brecha, N.C. (2010). Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells. European Journal of Neuroscience 31, 13881401.CrossRefGoogle ScholarPubMed
Liu, J., Li, G.-L. & Yang, X.-L. (2006). An ionotropic GABA receptor with novel pharmacology at bullfrog cone photoreceptor terminals. Neurosignals 15, 1325.CrossRefGoogle ScholarPubMed
Liu, J., Zhao, J.-W., Du, J.-L. & Yang, X.-L. (2005). Functional GABAB receptors are expressed at the cone photoreceptor terminals in bullfrog retina. Neuroscience 132, 103113.CrossRefGoogle Scholar
Liu, X., Hirano, A.A., Sun, X., Brecha, N.C. & Barnes, S. (2013). Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA- and pH-sensitive mechanism. Journal of Physiology (London) 591, 33093324.CrossRefGoogle ScholarPubMed
Olsen, R.W. & Sieghart, W. (2008). International union of pharmacology. LXX. Subtypes of γ-aminobutyric acid a receptors: Classification on the basis of subunit composition, pharmacology, and function. Update. Pharmacological Reviews 60, 243260.CrossRefGoogle ScholarPubMed
Pattnaik, B., Jellali, A., Sahel, J., Dreyfus, H. & Picaud, S. (2000). GABAC receptors are localized with microtubule-associated protein 1B in mammalian cone photoreceptors. Journal of Neuroscience 20, 67896796.CrossRefGoogle ScholarPubMed
Picaud, S., Pattnaik, B., Hicks, D., Forster, V., Fontaine, V., Sahel, J. & Dreyfus, H. (1998). GABAA and GABAC receptors in adult porcine cones: Evidence from a photoreceptor-glia co-culture model. Journal of Physiology (London) 513, 3342.CrossRefGoogle ScholarPubMed
Piccolino, M. (1995). The feedback synapse from horizontal cells to cone photoreceptors in the vertebrate retina. Progress in Retinal and Eye Research 14, 141196.CrossRefGoogle Scholar
Pottek, M., Hoppenstedt, W., Janssen-Bienhold, U., Schultz, K., Perlman, I. & Weiler, R. (2003). Contribution of connexin26 to electrical feedback inhibition in the turtle retina. Journal of Comparative Neurology 466, 468477.CrossRefGoogle ScholarPubMed
Schwartz, E.A. (1987). Depolarization without calcium can release gamma-aminobutyric acid from a retinal neuron. Science 238, 350355.CrossRefGoogle ScholarPubMed
Szmajda, B.A. & DeVries, S.H. (2011). Glutamate spillover between mammalian cone photoreceptors. Journal of Neuroscience 31, 1343113441.CrossRefGoogle ScholarPubMed
Tachibana, M. & Kaneko, A. (1984). Gamma-aminobutyric acid acts at axon terminals of turtle photoreceptors: Difference in sensitivity among cell types. Proceedings of the National Academy of Sciences of the United States of America 81, 79617964.CrossRefGoogle ScholarPubMed
Tatsukawa, T., Hirasawa, H., Kaneko, A. & Kaneda, M. (2005). GABA-mediated component in the feedback response of turtle retinal cones. Visual Neuroscience 22, 317324.CrossRefGoogle ScholarPubMed
Thoreson, W.B. & Bryson, E.J. (2004). Chloride equilibrium potential in salamander cones. BMC Neuroscience 5, 53.CrossRefGoogle ScholarPubMed
Thoreson, W.B. & Mangel, S.C. (2012). Lateral interactions in the outer retina. Progress in Retinal and Eye Research 31, 407441.CrossRefGoogle ScholarPubMed
Thoreson, W.B., Nitzan, R. & Miller, R.F. (2000). Chloride efflux inhibits single calcium channel open probability in vertebrate photoreceptors: Chloride imaging and cell-attached patch-clamp recordings. Visual Neuroscience 17, 197206.CrossRefGoogle ScholarPubMed
Vardi, N., Masarachia, P. & Sterling, P. (1992). Immunoreactivity to GABAA receptor in the outer plexiform layer of the cat retina. Journal of Comparative Neurology 320, 394397.CrossRefGoogle ScholarPubMed
Vardi, N. & Sterling, P. (1994). Subcellular localization of GABAA receptor on bipolar cells in macaque and human retina. Vision Research 34, 12351246.CrossRefGoogle ScholarPubMed
Versaux-Botteri, C., Pochet, R. & Nguyen-Legros, J. (1989). Immunohistochemical localization of GABA-containing neurons during postnatal development of the rat retina. Investigative Ophthalmology & Visual Science 30, 652659.Google ScholarPubMed
Verweij, J., Hornstein, E.P. & Schnapf, J.L. (2003). Surround antagonism in macaque cone photoreceptors. Journal of Neuroscience 23, 1024910257.CrossRefGoogle ScholarPubMed
Verweij, J., Kamermans, M. & Spekreijse, H. (1996). Horizontal cells feed back to cones by shifting the cone calcium-current activation range. Vision Research 36, 39433953.CrossRefGoogle ScholarPubMed
Vroman, R., Klaassen, L.J., Howlett, M.H.C., Cenedese, V., Klooster, J., Sjoerdsma, T. & Kamermans, M. (2014). Extracellular ATP hydrolysis inhibits synaptic transmission by increasing pH buffering in the synaptic cleft. PLoS Biology 12, e1001864.CrossRefGoogle ScholarPubMed
Wang, T-M., Holzhausen, L.C. & Kramer, R.H. (2014). Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina. Nature Neuroscience 17, 262268.CrossRefGoogle ScholarPubMed
Warren, T.J., Hook, M.J., Supuran, C.T. & Thoreson, W.B. (2016a). Sources of protons and a role for bicarbonate in inhibitory feedback from horizontal cells to cones in Ambystoma tigrinum retina. Journal of Physiology (London) 594, 66616677.CrossRefGoogle Scholar
Warren, T.J., Hook, M.J.V., Tranchina, D. & Thoreson, W.B. (2016b). Kinetics of inhibitory feedback from horizontal cells to photoreceptors: Implications for an ephaptic mechanism. Journal of Neuroscience 36, 1007510088.CrossRefGoogle Scholar
Wu, S.M. (1986). Effects of gamma-aminobutyric acid on cones and bipolar cells of the tiger salamander retina. Brain Research 365, 7077.CrossRefGoogle ScholarPubMed
Wu, S.M. (1992). Feedback connections and operation of the outer plexiform layer of the retina. Current Opinion in Neurobiology 2, 462468.CrossRefGoogle ScholarPubMed
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