Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Các khớp nối giữa các tế bào lưỡng cực phục vụ các đường truyền tín hiệu chính trong võng mạc người
Tóm tắt
Connexin36 (Cx36) là thành phần của các khớp nối khoảng trống (GJ) trên toàn bộ não, kết nối các neuron thành các đồng bộ chức năng. Tại võng mạc, chúng là cơ sở cho việc truyền tải, trung bình hóa và tương quan tín hiệu trước khi chuyển thông tin thị giác đến não. Đây là nghiên cứu đầu tiên mô tả các khớp nối GJ của tế bào lưỡng cực (BC) trong võng mạc trong, của người, mà chức năng của chúng vẫn còn bí ẩn ngay cả trong các mô hình động vật đã được nghiên cứu. Hơn nữa, một số đặc điểm độc đáo (ví dụ: fovea, trichromacy, hệ thống midget) đòi hỏi phải kiểm tra lại các kết quả từ mô hình động vật trong võng mạc người. Các mẫu người bảo quản tốt sau khi qua đời trong nghiên cứu này cho phép xác định hóa sinh các BC biểu hiện Cx36. Kết quả cho thấy rằng cả nội tế bào theo đường que và đường chóp đều thể hiện biểu hiện Cx36 mạnh mẽ. Đầu vào BC que tới các tế bào amacrine AII (AC) xuất hiện kế bên GJs AII, do đó gợi ý về việc BC que nhắm vào các tế bào AII theo cách chiến lược. Các BC chóp phục vụ cho các đường truyền tín hiệu midget, parasol hoặc koniocellular thể hiện rất nhiều Cx36 để hình thành các mạng lưới nối tương đồng. Ngoài ra, chúng cũng thiết lập các liên kết GJ dị đồng để phục vụ việc trao đổi thông tin giữa các dòng tín hiệu song song. Đáng chú ý, một biểu hiện Cx36 nổi bật được thể hiện bởi các BC của hệ thống midget, có vẻ như duy trì các liên lạc mật thiết với các BC hai lớp phục vụ cho các đường dẫn khác. Những phát hiện này gợi ý rằng các GJ của BC trong các dòng tín hiệu song song phục vụ cho cả việc trao đổi tín hiệu nội bộ và giữa các đường dẫn trong võng mạc người.
Từ khóa
#Connexin36 #khớp nối khoảng trống #tế bào lưỡng cực #võng mạc #tín hiệuTài liệu tham khảo
Alonso JM, Usrey WM, Reid RC (1996) Precisely correlated firing in cells of the lateral geniculate nucleus. Nature 383:815–819
Arai I, Tanaka M, Tachibana M (2010) Active roles of electronically coupled bipolar cell network in the adult retina. J Neurosci 30:9260–9270. doi:10.1523/JNEUROSCI.1590-10.2010
Bloomfield SA, Dacheux RF (2001) Rod vision: pathways and processing in the mammalian retina. Prog Retin Eye Res 20:351–384
Bloomfield SA, Völgyi B (2009) The diverse functional roles and regulation of neuronal gap junctions in the retina. Nat Rev Neurosci 10:495–506. doi:10.1038/nrn2636
Chen YY, Liu SL, Hu DP, Xing YQ, Shen Y (2014) N-methyl-N -nitrosourea induced retinal degeneration in mice. Exp Eye Res 121:102–113. doi:10.1016/j.exer.2013.12.019
Cohen E, Sterling P (1990) Cenvergence and divergence of cones onto bipolar cells in the central area of cat retina. Philos Trans R Soc Lond B Biol Sci 330:323–328
Dacey D, Packer OS, Diller L, Brainard D, Peterson B, Lee B (2000) Center surround receptive field structure of cone bipolar cells in primate retina. Vision Res 40:1801–1811
Dacey DM, Peterson BB, Robinson FR, Gamlin PD (2003) Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN-projecting ganglion cell types. Neuron 37:15–27
Dacey DM, Crook JD, Packer OS (2014) Distinct synaptic mechanisms create parallel S-ON and S-OFF color opponent pathways in the primate retina. Vis Neurosci 31:139–151. doi:10.1017/S0952523813000230
Deans MR, Völgyi B, Goodenough DA, Bloomfield SA, Paul DL (2002) Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Neuron 36:703–712
Eliasieh K, Liets LC, Chalupa LM (2007) Cellular reorganization in the human retina during normal aging. Invest Ophthalmol Vis Sci 48:2824–2830
Famiglietti EV, Kolb H (1975) A bistratified amacrine cell and synaptic circuitry in the inner plexiform layer of the retina. Brain Res 84:293–300
Feigenspan A, Teubner B, Willecke K, Weiler R (2001) Expression of neuronal connexin36 in AII amacrine cells of the mammalian retina. J Neurosci 21:230–239
Feigenspan A, Janssen-Bienhold U, Hormuzdi S, Monyer H, Degen J, Söhl G, Willecke K, Ammermüller J, Weiler R (2004) Expression of connexin36 in cone pedicles and OFF-cone bipolar cells of the mouse retina. J Neurosci 24:3325–3334
Ghosh KK, Martin PR, Grünert U (1997) Morphological analysis of the blue cone pathway in the retina of a New World monkey, the marmoset Callithrix jacchus. J Comp Neurol 379:211–225
Ghosh KK, Bujan S, Haverkamp S, Feigenspan A, Wässle H (2004) Types of bipolar cells in the mouse retina. J Comp Neurol 469:70–82
Grünert U, Martin PR, Wässle H (1994) Immunocytochemical analysis of bipolar cells in the macaque monkey retina. J Comp Neurol 348:607–627
Güldenagel M, Söhl G, Plum A, Traub O, Teubner B, Weiler R, Willecke KS (2000) Expression patterns of connexin genes in mouse retina. J Comp Neurol 425:193–201
Güldenagel M, Ammermüller J, Feigenspan A, Teubner B, Degen J, Söhl G, Willecke K, Weiler R (2001) Visual transmission deficits in mice with targeted disruption of the gap junction gene connexin36. J Neurosci 21:6036–6044
Han Y, Massey SC (2005) Electrical synapses in retinal ON cone bipolar cells: subtype-specific expression of connexins. PNAS 102:13313–13318
Haverkamp S, Haeseleer F, Hendrickson A (2003) A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina. Visual Neurosci 20:589–600
Hidaka S, Akahori Y, Kurosawa Y (2004) Dendrodendritic electrical synapses between mammalian retinal ganglion cells. J Neurosci 24:10553–10567
Hombach S, Janssen-Bienhold U, Söhl G, Schubert T, Büssow H, Ott T, Weiler R, Willecke K (2004) Functional expression of connexin57 in horizontal cells of the mouse retina. Eur J Neurosci 19:2633–2640
Hunyady B, Krempels K, Harta G, Mezey E (1996) Immunohistochemical signal amplification by catalyzed reporter deposition and its application in double immunostaining. J Histochem Cytochem 44:1353–1362
Jacobs AL, Werblin FS (1998) Spatiotemporal patterns at the retinal output. J Neurophysiol 80:447–451
Jacoby RA, Marshak DW (2000) Synaptic connections of DB3 diffuse bipolar cell axons in macaque retina. J Comp Neurol 416:19–29
Jacoby R, Stafford D, Kouyama N, Marshak D (1996) Synaptic inputs to ON parasol ganglion cells in the primate retina. J Neurosci 16:8041–8056
Jacoby RA, Wiechmann AF, Amara SG, Leighton BH, Marshak DW (2000) Diffuse bipolar cell provide input to OFF parasol ganglion cells in the macaque retina. J Comp Neurol 416:6–18
Jusuf PR, Lee SCS, Grünert U (2004) Synaptic connectivity of the diffuse bipolar cell type DB6 in the inner plexiform layer of primate retina. J Comp Neurol 469:494–506
Kántor O, Benkő Z, Énzsöly A, Dávid C, Naumann A, Nitschke R, Szabó A, Pálfi E, Orbán J, Nyitrai M, Németh J, Szél Á, Lukáts Á, Völgyi B (2016a) Characterization of connexin36 gap junctions in the human outer retina. Brain Struct Funct 221:2963–2984. doi:10.1007/s00429-015-1082-z
Kántor O, Mezey S, Adeghate J, Naumann A, Nitschke R, Énzsöly A, Szabó A, Lukáts Á, Németh J, Somogyvári Z, Völgyi B (2016b) Calcium buffer proteins are specific markers of human retinal neurons. Cell Tissue Res 365:29–50. doi:10.1007/s00441-016-2376-z
Kántor O, Varga A, Tóth R, Énzsöly A, Pálfi E, Kovács-Öller T, Nitschke R, Szél Á, Székely A, Völgyi B, Négyessy L, Somogyvári Z, Lukáts Á (2015) Stratified organization and disorganization of inner plexiform layer revealed by TNAP activity in healthy and diabetic rat retina. Cell Tissue Res 359(2):409–421. doi:10.1007/s00441-014-2047-x
Kihara AH, Mantovani de Castro L, Belmonte MA, Yan CY, Moriscot AS, Hamassaki DE (2006) Expression of connexins 36, 43, and 45 during postnatal development of the mouse retina. J Neurobiol 66:1397–1410
Kihara AH, Santos TO, Osuna-Melo EJ, Paschon V, Vidal KS, Akamine PS, Castro LM, Resende RR, Hamassaki DE, Britto LR (2010) Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis. Int J Dev Neurosci 28:39–52. doi:10.1016/j.ijdevneu.2009.09.006
Kolb H, Linberg KA, Fischer SK (1992) Neurons of the human retina: A Golgi study. J Comp Neurol 318:147–187
Kovács-Öller T, Debertin G, Raics K, Orbán J, Nyitrai M, Völgyi B (2014) Developmental changes in the expression level of connexin36 in the rat retina. Cell Tissue Res 358:289–302. doi:10.1007/s00441-014-1967-9
Kuo SP, Schwartz GW, Rieke F (2016) Nonlinear spatiotemporal integration by electrical and chemical synapses in the retina. Neuron 90:320–332. doi:10.1016/j.neuron.2016.03.012
Lee EJ, Han JW, Kim HJ, Kim IB, Lee MY, Oh SJ, Chung JW, Chun MH (2003) The immunocytochemical localization of connexin 36 at rod and cone gap junctions in the guinea pig retina. Eur J Neurosci 18:2925–2934
Lee SC, Weltzien F, Madigan MC, Martin PR, Grünert U (2016) Identification of AII amacrine, displaced amacrine, and bistratified ganglion cell types in human retina with antibodies against calretinin. J Comp Neurol 524:39–53. doi:10.1002/cne.23821
Li W, Zhang J, Massey SC (2002) Coupling pattern of S1 and S2 amacrine cells in the rabbit retina. Vis Neurosci 19(2):119–131
Lin B, Jakobs TC, Masland RH (2005) Different functional types of bipolar cells use different gap- junctional proteins. J Neurosci 25:6696–6701
Luo X, Ghosh KK, Martin PR, Grünert U (1999) Analysis of two types of cone bipolar cells in the retina of a New World monkey, the marmoset, Callithrix jacchus. Vis Neurosci 16:707–719
Marc RE, Liu WL, Müller JF (1988) Gap junctions in the inner plexiform layer of the goldfish retina. Vision Res 28:9–24
Marc RE, Jones BW, Watt CB, Anderson JR, Sigulinsky C, Lauritzen S (2013) Retinal connectomics: towards complete, accurate networks. Prog Retin Eye Res 37:141–162. doi:10.1016/j.preteyeres.2013.08.002
Marshak DW, Yamada ES, Bordt AS, Perryman WC (2002) Synaptic input to an ON parasol ganglion cell in the macaque retina: a serial section analysis. Vis Neurosci 19:299–305
Masland D (2011) Cell Populations of the retina: the proctor lecture. Investig Ophthalmol Vis Sci 52:4581–4591
Masri RA, Percival KA, Koizumi A, Martin PR, Grünert U (2016) Connectivity between the OFF bipolar type DB3a and six types of ganglion cell in the marmoset retina. J Comp Neurol 524:1839–1858. doi:10.1002/cne.23925
Massey SC, O’Brien JJ, Trexler EB, Li W, Keung JW, Mills SL, O’Brien J (2003) Multple neuronal connexins in the mammalian retina. Cell Commun Adhes 10:425–430
Maxeiner S, Dedek K, Janssen-Bienhold U, Ammermüller J, Brune H, Kirsch T, Pieper M, Degen J, Krüger O, Willecke K, Weiler R (2005) Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impared visual transmission. J Neurosci 25:566–576
Mills SL (1999) Unusual coupling patterns of a cone bipolar cell in the rabbit retina. Vis Neurosci 16:1029–1035
Mills SL, O’Brien JJ, Li W, O’Brien J, Massey SC (2001) Rod pathways in the mammalian retina use connexin36. J Comp Neurol 436:336–350
Müller LP, Dedek K, Janssen-Bienhold U, Meyer A, Kreuzberg MM, Lorenz S, Willecke K, Weiler R (2010) Expression and modulation of connexin 30.2, a novel gap junction protein in the mouse retina. Vis Neurosci 27:91–101. doi:10.1017/S0952523810000131
Nelson R (1982) AII amacrine cells quicken time course of rod signals in the cat retina. J Neurophysiol 47:928–947
O’Brien JJ, Chen X, Macleish PR, O’Brien J, Massey SC (2012) Photoreceptor coupling mediated by connexin36 in the primate retina. J Neurosci 32:4675–4687. doi:10.1523/JNEUROSCI.4749-11.2012
Pan F, Paul DL, Bloomfield SA, Völgyi B (2010) Connexin36 is required for gap junctional coupling of most ganglion cell subtypes in the mouse retina. J Comp Neurol 518:911–927. doi:10.1002/cne.22254
Percival KA, Martin PR, Grünert U (2011) Synaptic inputs to two types of koniocellular pathway ganglion cells in marmoset retina. J Comp Neurol 519:2135–2153. doi:10.1002/cne.22586
Percival KA, Martin PR, Grünert U (2013) Organisation of koniocellular-projecting ganglion cells and diffuse bipolar cells in the primate fovea. Eur J Neurosci 37:1072–1089. doi:10.1111/ejn.12117
Percival KA, Koizumi A, Masri RA, Buzás P, Martin PR, Grünert U (2014) Identification of a pathway from the retina to koniocellular layer K1 in the lateral geniculate nucleus of marmoset. J Neurosci 34:3821–3825. doi:10.1523/JNEUROSCI.4491-13.2014
Pereda A, O’Brien JO, Nagy JI, Bukauskas F, Davidson KGV, Kamasawa N, Yasumura T, Rash JE (2003) Connexin35 mediates electrical transmission at mixed synapses on Mauthner cells. J Neurosci 23:7489–7503
Petrasch-Parwez E, Habbes HW, Weickert S, Löbbecke-Schumacher M, Striedinger K, Wieczorek S, Dermietzel R, Epplen JT (2004) Fine-structural analysis and connexin expression in the retina of a transgenic model of Huntington’s disease. J Comp Neurol 479:181–197
Puthussery T, Gayet-Primo J, Taylor WR (2010) Localization of the calcium-binding protein secretagogin in cone bipolar cells of the mammalian retina. J Comp Neurol 518:513–525. doi:10.1002/cne.22234
Rash JE, Kamasawa N, Davidson KGV, Yasumura T, Pereda AE, Nagy JI (2012) Connexin composition in apposed gap junction hemiplaques revealed by matched double-replica freeze-fracture replica immunogold labeling. J Membr Biol 245:333–344. doi:10.1007/s00232-012-9454-2
Raviola E, Gilula NB (1975) Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. A freeze-fracture study in monkeys and rabbits. J Cell Biol 65:192–222
Regus-Leidig H, Specht D, Tom Dieck S, Brandstätter JH (2010) Stability of active zone components at the photoreceptor ribbon complex. Mol Vis 16:2690–2700
Regus-Leidig H, Fuchs M, Löhner M, Leist SR, Leal-Ortiz S, Chiodo VA, Hauswirth WW, Garner CC, Brandstätter JH (2014) In vivo knockdown of Piccolino disrupts presynaptic ribbon morphology in mouse photoreceptor synapses. Front Cell Neurosci 8:259. doi:10.3389/fncel.2014.00259
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. doi:10.1038/nmeth.2019
Schubert T, Degen J, Willecke K, Hormuzdi SG, Monyer H, Weiler R (2005a) Connexin36 mediates gap junctional coupling of alpha-ganglion cells in mouse retina. J Comp Neurol 485:191–201
Schubert T, Maxeiner S, Krüger O, Willecke K, Weiler R (2005b) Connexin45 mediates gap junctional coupling of bistratified ganglion cells in the mouse retina. J Comp Neurol 490:29–39
Söhl G, Joussen A, Kociok N, Willecke K (2010) Expression of connexin genes in the human retina. BMC Ophthalmol 10:27. doi:10.1186/1471-2415-10-27
Toader O, Forte N, Orlando M, Ferrea E, Raimondi A, Baldelli P, Benfenati F, Medrihan L (2013) Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures. Front Cell Neurosci 7:138. doi:10.3389/fncel.2013.00138
Tomassy GS, Morello N, Calcagno E, Giustetto M (2014) Developmental abnormalities of cortical interneurons precede symptoms onset in a mouse model of Rett syndrome. J Neurochem 131:115–127. doi:10.1111/jnc.12803
Tsukamoto Y, Omi N (2015) OFF bipolar cells in macaque retina: type-specific connectivity in the outer and inner synaptic layers. Front Neuroanat 9:122 doi:10.3389/fnana.2015.00122
Umino O, Maehara M, Hidaka S, Kita S, Hashimoto Y (1994) The network properties of bipolar-bipolar cell coupling in the retina of teleost fishes. Vis Neurosci 11:533–548
Usrey WM, Reid RC (1999) Synchronous activity in the visual system. Annu Rev Physiol 61:435–456
Van Haesendonck E, Missotten L (1983) Interbipolar contacts in the dorsal inner plexiform layer in the retina of Callionymus lyra L. J Ultrastruct Res 83:303–311
Vaney DI (1997) Neuronal coupling in rod-signal pathways of the retina. Invest Ophthalmol Vis Sci 38(2):267–273
Völgyi B, Deans MR, Paul DL, Bloomfield SA (2004) Convergence and segregation of the multiple rod pathways in mammalian retina. J Neurosci 24:11182–11192
Völgyi B, Abrams J, Paul DL, Bloomfield SA (2005) Morphology and tracer coupling pattern of alpha ganglion cells in the mouse retina. J Comp Neurol 492:66–77
Völgyi B, Chheda S, Bloomfield SA (2009) Tracer coupling patterns of the ganglion cell subtypes in the mouse retina. J Comp Neurol 512:664–687. doi:10.1002/cne.21912
Völgyi B, Kovács-Oller T, Atlasz T, Wilhelm M, Gábriel R (2013a) Gap junctional coupling in the vertebrate retina: variations on one theme? Prog Retin Eye Res 34:1–18. doi:10.1016/j.preteyeres.2012.12.002
Völgyi B, Pan F, Paul DL, Wang JT, Huberman AD, Bloomfield SA (2013b) Gap junctions are essential for generating the correlated spike activity of neighboring retinal ganglion cells. PLoS One 8:e69426. doi:10.1371/journal.pone.0069426
Weltzien F, Dimarco S, Protti DA, Daraio T, Martin PR, Grünert U (2014) Characterization of secretagogin-immunoreactive amacrine cells in marmoset retina. J Comp Neurol 522:435–455. doi:10.1002/cne.23420