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Structure and function of the gap junctional network of photoreceptive ganglion cells

Published online by Cambridge University Press:  16 September 2021

Xiwu Zhao  and
Kwoon Y. Wong
Xiwu Zhao
Affiliation:
Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA
Kwoon Y. Wong*
Affiliation:
Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA
*
*Corresponding author: Kwoon Y. Wong, email: kwoon@umich.edu
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Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only anterogradely to drive behavioral responses, but also retrogradely to some amacrine interneurons to modulate retinal physiology. We previously found that all displaced amacrine cells with spiking, tonic excitatory photoresponses receive gap-junction input from ipRGCs, but the connectivity patterns and functional roles of ipRGC-amacrine coupling remained largely unknown. Here, we injected PoPro1 fluorescent tracer into all six types of mouse ipRGCs to identify coupled amacrine cells, and analyzed the latter’s morphological and electrophysiological properties. We also examined how genetically disrupting ipRGC-amacrine coupling affected ipRGC photoresponses. Results showed that ipRGCs couple with not just ON- and ON/OFF-stratified amacrine cells in the ganglion-cell layer as previously reported, but also OFF-stratified amacrine cells in both ganglion-cell and inner nuclear layers. M1- and M3-type ipRGCs couple mainly with ON/OFF-stratified amacrine cells, whereas the other ipRGC types couple almost exclusively with ON-stratified ones. ipRGCs transmit melanopsin-based light responses to at least 93% of the coupled amacrine cells. Some of the ON-stratifying ipRGC-coupled amacrine cells exhibit transient hyperpolarizing light responses. We detected bidirectional electrical transmission between an ipRGC and a coupled amacrine cell, although transmission was asymmetric for this particular cell pair, favoring the ipRGC-to-amacrine direction. We also observed electrical transmission between two amacrine cells coupled to the same ipRGC. In both scenarios of coupling, the coupled cells often spiked synchronously. While ipRGC-amacrine coupling somewhat reduces the peak firing rates of ipRGCs’ intrinsic melanopsin-based photoresponses, it renders these responses more sustained and longer-lasting. In summary, ipRGCs’ gap junctional network involves more amacrine cell types and plays more roles than previously appreciated.

Keywords

melanopsinipRGCamacrine cellgap junctionaction potential
Type
Research Article
Information
Visual Neuroscience , Volume 38 , 2021 , E014
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Aboelela, S.W. & Robinson, D.W. (2004). Physiological response properties of displaced amacrine cells of the adult ferret retina. Visual Neuroscience 21, 135–144.CrossRefGoogle ScholarPubMed
Apostolides, P.F. & Trussell, L.O. (2013). Regulation of interneuron excitability by gap junction coupling with principal cells. Nature Neuroscience 16, 1764–1772.CrossRefGoogle ScholarPubMed
Aranda, M.L. & Schmidt, T.M. (2021). Diversity of intrinsically photosensitive retinal ganglion cells: Circuits and functions. Cellular and Molecular Life Sciences 78, 889–907.CrossRefGoogle ScholarPubMed
Barlow, H.B. & Levick, W.R. (1969). Changes in the maintained discharge with adaptation level in the cat retina. The Journal of Physiology 202, 699–718.CrossRefGoogle ScholarPubMed
Barnard, A.R., Hattar, S., Hankins, M.W. & Lucas, R.J. (2006). Melanopsin regulates visual processing in the mouse retina. Current Biology 16, 389–395.CrossRefGoogle ScholarPubMed
Brivanlou, I.H., Warland, D.K. & Meister, M. (1998). Mechanisms of concerted firing among retinal ganglion cells. Neuron 20, 527–539.CrossRefGoogle ScholarPubMed
Connors, B.W. (2017). Synchrony and so much more: Diverse roles for electrical synapses in neural circuits. Developmental Neurobiology 77, 610–624.CrossRefGoogle ScholarPubMed
Dacey, D.M., Liao, H.W., Peterson, B.B., Robinson, F.R., Smith, V.C., Pokorny, J., Yau, K.W. & Gamlin, P.D. (2005). Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 433, 749–754.CrossRefGoogle ScholarPubMed
Dkhissi-Benyahya, O., Coutanson, C., Knoblauch, K., Lahouaoui, H., Leviel, V., Rey, C., Bennis, M. & Cooper, H.M. (2013). The absence of melanopsin alters retinal clock function and dopamine regulation by light. Cellular and Molecular Life Sciences 70, 3435–3447.CrossRefGoogle Scholar
Dumitrescu, O.N., Pucci, F.G., Wong, K.Y. & Berson, D.M. (2009). Ectopic retinal ON bipolar cell synapses in the OFF inner plexiform layer: Contacts with dopaminergic amacrine cells and melanopsin ganglion cells. The Journal of Comparative Neurology 517, 226–244.CrossRefGoogle ScholarPubMed
Ecker, J.L., Dumitrescu, O.N., Wong, K.Y., Alam, N.M., Chen, S.K., LeGates, T., Renna, J.M., Prusky, G.T., Berson, D.M. & Hattar, S. (2010). Melanopsin-expressing retinal ganglion-cell photoreceptors: Cellular diversity and role in pattern vision. Neuron 67, 49–60.CrossRefGoogle ScholarPubMed
Emanuel, A.J. & Do, M.T. (2015). Melanopsin tristability for sustained and broadband phototransduction. Neuron 85, 1043–1055.CrossRefGoogle ScholarPubMed
Estevez, M.E., Fogerson, P.M., Ilardi, M.C., Borghuis, B.G., Chan, E., Weng, S., Auferkorte, O.N., Demb, J.B. & Berson, D.M. (2012). Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. The Journal of Neuroscience 32, 13608–13620.CrossRefGoogle ScholarPubMed
Galarreta, M. & Hestrin, S. (2001). Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295–2299.CrossRefGoogle ScholarPubMed
Hankins, M.W. & Lucas, R.J. (2002). The primary visual pathway in humans is regulated according to long-term light exposure through the action of a nonclassical photopigment. Current Biology 12, 191–198.CrossRefGoogle ScholarPubMed
Harrison, K.R., Chervenak, A.P., Resnick, S.M., Reifler, A.N. & Wong, K.Y. (2021a). Amacrine cells forming gap junctions with intrinsically photosensitive retinal ganglion cells: ipRGC types, neuromodulator contents, and Connexin isoform. Investigative Ophthalmology & Visual Science 62, 10.CrossRefGoogle Scholar
Harrison, K.R., Reifler, A.N., Chervenak, A.P. & Wong, K.Y. (2021b). Prolonged melanopsin-based photoresponses depend in part on RPE65 and cellular retinaldehyde-binding protein (CRALBP). Current Eye Research 46, 515–523.CrossRefGoogle Scholar
Hatori, M., Le, H., Vollmers, C., Keding, S.R., Tanaka, N., Buch, T., Waisman, A., Schmedt, C., Jegla, T. & Panda, S. (2008). Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. PLoS One 3, e2451.CrossRefGoogle ScholarPubMed
Hoshi, H., Liu, W.L., Massey, S.C. & Mills, S.L. (2009). ON inputs to the OFF layer: Bipolar cells that break the stratification rules of the retina. The Journal of Neuroscience 29, 8875–8883.CrossRefGoogle ScholarPubMed
Hoshi, H., O’Brien, J. & Mills, S.L. (2006). A novel fluorescent tracer for visualizing coupled cells in neural circuits of living tissue. The Journal of Histochemistry and Cytochemistry 54, 1169–1176.CrossRefGoogle ScholarPubMed
Hu, C., Hill, D.D. & Wong, K.Y. (2013). Intrinsic physiological properties of the five types of mouse ganglion-cell photoreceptors. Journal of Neurophysiology 109, 1876–1889.CrossRefGoogle ScholarPubMed
Hu, E.H. & Bloomfield, S.A. (2003). Gap junctional coupling underlies the short-latency spike synchrony of retinal alpha ganglion cells. The Journal of Neuroscience 23, 6768–6777.CrossRefGoogle ScholarPubMed
Jacoby, J., Zhu, Y., DeVries, S.H. & Schwartz, G.W. (2015). An Amacrine cell circuit for signaling steady illumination in the retina. Cell Reports 13, 2663–2670.CrossRefGoogle ScholarPubMed
Jia, Y., Lee, S., Zhuo, Y. & Zhou, Z.J. (2020). A retinal circuit for the suppressed-by-contrast receptive field of a polyaxonal amacrine cell. Proceedings of the National Academy of Sciences of the United States of America 117, 9577–9583.CrossRefGoogle ScholarPubMed
Jin, N., Zhang, Z., Keung, J., Youn, S.B., Ishibashi, M., Tian, L.M., Marshak, D.W., Solessio, E., Umino, Y., Fahrenfort, I., Kiyama, T., Mao, C.A., You, Y., Wei, H., Wu, J., Postma, F., Paul, D.L., Massey, S.C. & Ribelayga, C.P. (2020). Molecular and functional architecture of the mouse photoreceptor network. Science Advances 6, eaba7232.CrossRefGoogle ScholarPubMed
Maimon, G. & Assad, J.A. (2009). Beyond Poisson: Increased spike-time regularity across primate parietal cortex. Neuron 62, 426–440.CrossRefGoogle ScholarPubMed
Manor, Y., Rinzel, J., Segev, I. & Yarom, Y. (1997). Low-amplitude oscillations in the inferior olive: A model based on electrical coupling of neurons with heterogeneous channel densities. Journal of Neurophysiology 77, 2736–2752.CrossRefGoogle Scholar
Meister, M. & Berry, M.J. 2nd. (1999). The neural code of the retina. Neuron 22, 435–450.CrossRefGoogle ScholarPubMed
Milner, E.S. & Do, M.T.H. (2017). A population representation of absolute light intensity in the mammalian retina. Cell 171, 865–876 e816.CrossRefGoogle ScholarPubMed
Milosavljevic, N., Storchi, R., Eleftheriou, C.G., Colins, A., Petersen, R.S. & Lucas, R.J. (2018). Photoreceptive retinal ganglion cells control the information rate of the optic nerve. Proceedings of the National Academy of Sciences of the United States of America 115, E11817–E11826.CrossRefGoogle ScholarPubMed
Muller, L.P., Do, M.T., Yau, K.W., He, S. & Baldridge, W.H. (2010). Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina. The Journal of Comparative Neurology 518, 4813–4824.CrossRefGoogle ScholarPubMed
Mure, L.S., Hatori, M., Zhu, Q., Demas, J., Kim, I.M., Nayak, S.K. & Panda, S. (2016). Melanopsin-encoded response properties of intrinsically photosensitive retinal ganglion cells. Neuron 90, 1016–1027.CrossRefGoogle ScholarPubMed
Park, S.J.H., Pottackal, J., Ke, J.B., Jun, N.Y., Rahmani, P., Kim, I.J., Singer, J.H. & Demb, J.B. (2018). Convergence and divergence of CRH Amacrine cells in mouse retinal circuitry. The Journal of Neuroscience 38, 3753–3766.CrossRefGoogle ScholarPubMed
Perez De Sevilla Muller, L., Shelley, J. & Weiler, R. (2007). Displaced amacrine cells of the mouse retina. The Journal of Comparative Neurology 505, 177–189.CrossRefGoogle ScholarPubMed
Pottackal, J., Walsh, H.L., Rahmani, P., Zhang, K., Justice, N.J. & Demb, J.B. (2021). Photoreceptive ganglion cells drive circuits for local inhibition in the mouse retina. The Journal of Neuroscience 41, 1489–1504.CrossRefGoogle ScholarPubMed
Prigge, C.L., Yeh, P.T., Liou, N.F., Lee, C.C., You, S.F., Liu, L.L., McNeill, D.S., Chew, K.S., Hattar, S., Chen, S.K. & Zhang, D.Q. (2016). M1 ipRGCs influence visual function through retrograde signaling in the retina. The Journal of Neuroscience 36, 7184–7197.CrossRefGoogle ScholarPubMed
Quattrochi, L.E., Stabio, M.E., Kim, I., Ilardi, M.C., Michelle Fogerson, P., Leyrer, M.L. & Berson, D.M. (2019). The M6 cell: A small-field bistratified photosensitive retinal ganglion cell. The Journal of Comparative Neurology 527, 297–311.CrossRefGoogle ScholarPubMed
Reifler, A.N., Chervenak, A.P., Dolikian, M.E., Benenati, B.A., Li, B.Y., Wachter, R.D., Lynch, A.M., Demertzis, Z.D., Meyers, B.S., Abufarha, F.S., Jaeckel, E.R., Flannery, M.P. & Wong, K.Y. (2015). All spiking, sustained ON displaced amacrine cells receive gap-junction input from melanopsin ganglion cells. Current Biology 25, 2763–2773.CrossRefGoogle ScholarPubMed
Sabbah, S., Berg, D., Papendorp, C., Briggman, K.L. & Berson, D.M. (2017). A Cre mouse line for probing irradiance- and direction-encoding retinal networks. eNeuro 4, ENEURO.0065-17.2017.CrossRefGoogle ScholarPubMed
Schmidt, T.M. & Kofuji, P. (2011). Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse. The Journal of Comparative Neurology 519, 1492–1504.CrossRefGoogle ScholarPubMed
Sekaran, S., Foster, R.G., Lucas, R.J. & Hankins, M.W. (2003). Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons. Current Biology 13, 1290–1298.CrossRefGoogle ScholarPubMed
Sondereker, K.B., Stabio, M.E. & Renna, J.M. (2020). Crosstalk: The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image-forming and non-image-forming vision. The Journal of Comparative Neurology 528, 2044–2067.CrossRefGoogle ScholarPubMed
Stabio, M.E., Sabbah, S., Quattrochi, L.E., Ilardi, M.C., Fogerson, P.M., Leyrer, M.L., Kim, M.T., Kim, I., Schiel, M., Renna, J.M., Briggman, K.L. & Berson, D.M. (2018). The M5 cell: A color-opponent intrinsically photosensitive retinal ganglion cell. Neuron 97, 150–163 e154.CrossRefGoogle ScholarPubMed
Stinchcombe, A.R., Hu, C., Walch, O.J., Faught, S.D., Wong, K.Y. & Forger, D.B. (2021). M1-type, but not M4-type, melanopsin ganglion cells are physiologically tuned to the central circadian clock. Frontiers in Neuroscience 15, 652996.CrossRefGoogle Scholar
Usrey, W.M. & Reid, R.C. (1999). Synchronous activity in the visual system. Annual Review of Physiology 61, 435–456.CrossRefGoogle ScholarPubMed
Veruki, M.L. & Hartveit, E. (2002). AII (rod) amacrine cells form a network of electrically coupled interneurons in the mammalian retina. Neuron 33, 935–946.CrossRefGoogle Scholar
Viney, T.J., Balint, K., Hillier, D., Siegert, S., Boldogkoi, Z., Enquist, L.W., Meister, M., Cepko, C.L. & Roska, B. (2007). Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Current Biology 17, 981–988.CrossRefGoogle ScholarPubMed
Wong, K.Y. (2012). A retinal ganglion cell that can signal irradiance continuously for 10 hours. The Journal of Neuroscience 32, 11478–11485.CrossRefGoogle ScholarPubMed
Zhang, D.Q., Wong, K.Y., Sollars, P.J., Berson, D.M., Pickard, G.E. & McMahon, D.G. (2008). Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons. Proceedings of the National Academy of Sciences of the United States of America 105, 14181–14186.CrossRefGoogle ScholarPubMed
Zhao, X., Pack, W., Khan, N.W. & Wong, K.Y. (2016). Prolonged inner retinal photoreception depends on the visual retinoid cycle. The Journal of Neuroscience 36, 4209–4217.CrossRefGoogle ScholarPubMed
Zhao, X., Reifler, A.N., Schroeder, M.M., Jaeckel, E.R., Chervenak, A.P. & Wong, K.Y. (2017a). Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells. The Journal of General Physiology 149, 335–353.CrossRefGoogle Scholar
Zhao, X., Stafford, B.K., Godin, A.L., King, W.M. & Wong, K.Y. (2014). Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells. The Journal of Physiology 592, 1619–1636.CrossRefGoogle ScholarPubMed
Zhao, X., Wong, K.Y. & Zhang, D.Q. (2017b). Mapping physiological inputs from multiple photoreceptor systems to dopaminergic amacrine cells in the mouse retina. Scientific Reports 7, 7920.CrossRefGoogle Scholar