Characterization of connexin36 gap junctions in the human outer retina
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Retinal connexins (Cx) form gap junctions (GJ) in key circuits that transmit average or synchronize signals. Expression of Cx36, -45, -50 and -57 have been described in many species but there is still a disconcerting paucity of information regarding the Cx makeup of human retinal GJs. We used well-preserved human postmortem samples to characterize Cx36 GJ constituent circuits of the outer plexiform layer (OPL). Based on their location, morphometric characteristics and co-localizations with outer retinal neuronal markers, we distinguished four populations of Cx36 plaques in the human OPL. Three of these were comprised of loosely scattered Cx36 plaques; the distalmost population 1 formed cone-to-rod GJs, population 2 in the mid-OPL formed cone-to-cone GJs, whereas the proximalmost population 4 likely connected bipolar cell dendrites. The fourth population (population 3) of Cx36 plaques conglomerated beneath cone pedicles and connected dendritic tips of bipolar cells that shared a common presynaptic cone. Overall, we show that the human outer retina displays a diverse cohort of Cx36 GJ that follows the general mammalian scheme and display a great functional diversity.
KeywordsGap junction Electrical synapse Photoreceptor Cone Rod Bipolar cell
The authors thank to Zsuzsanna Vidra for her technical help and are grateful to Dr. Mark Eyre for the assistance with the English language. The authors are thankful for providing the antibodies: Noga Vardi (mGluR6), Wilhelm Koch (recoverin), Alán Alpár (guinea pig calbindin), Norbert Hájos (GluA4N). Supported by OTKA K105247 to B.V. and OTKA 73000 Á.S. This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’.to B.V. Finally, B.V. was also supported by the Hungarian Brain Research Program (KTIA_NAP_13-2-2015-0008).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (number of permission: TUKEB 58/2006) and with the 1964 Helsinki declaration and its later amendments.
- Kántor O, Temel Y, Holzmann C, Raber K, Nguyen HP, Cao C, Türkoglu HO, Rutten BP, Visser-Vandewalle V, Steinbusch HW et al (2006) Selective striatal neuron loss and alterations in behavior correlate with impaired striatal function in Huntington’s disease transgenic rats. Neurobiol Dis 22:538–547CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- Maxeiner S, Dedek K, Janssen-Bienhold U, Ammermüller J, Brune H, Kirsch T, Pieper M, Degen J, Krüger O, Willecke K et al (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 impaired visual transmission. J Neurosci 25:566–576CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- Sage D (2008) Watershed segmentation. Ecole Polytechnique Fédérale de Lausanne. http://bigwww.epfl.ch/sage/soft/watershed