Electrical synapses in rod and cone pathways of the mouse retina
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
The mammalian retina is able to encode visual information over ~10 log units of light intensities. It therefore has evolved two types of photoreceptors: rods for vision under dim light and cones for vision under bright light and color vision. Electrical synapses (gap junctions) built from connexin proteins play an essential role in the most sensitive rod pathway, the primary rod pathway, and in cone pathways. In the primary rod pathway, dim light signals are mediated from rods to rod bipolar cells, which in turn contact AII amacrine cells. AII cells form homocellular gap junctions among each other, thereby optimizing signal-to-noise ratio when photons are scarce. AII cells send the rod signal via glycinergic synapses to OFF cone bipolar cells and via heterocellular gap junctions to ON cone bipolar cells. Additionally, another small-field amacrine cell makes gap junctions with ON cone bipolar cells, the A8 cell. In this project, we aimed to determine the molecular basis for the differences in structure, assembly, and light-dependent modulation of homo- and heterocellular AII gap junctions and A8 gap junctions. To achieve our goals, we used co-immunoprecipitation, tracer coupling experiments, and (super-resolution) microscopy-based quantitative analyses of connexin localization. We found that AII amacrine cells express not only connexin36 but also connexin30.2 and showed that the two connexins are able to form heteromeric gap junctions. However, the role of connexin30.2 in AII cells remains enigmatic because the deletion of connexin30.2 did not impair the rod pathway in any way. As AII gap junctions were shown to be regulated by CaMKII in an activity-dependent manner, we determined the CaMKII isoform involved in this process. We found that expression of CaMKII isoforms is cell-type specific in the retina, with CaMKII-δ being the dominant isoform in AII cells and CaMKII-β in A8 cells. A8 and AII cells did not only differ in the CaMKII isoform they express but also in coupling partners, gap junction number, and gap junction modulation. In summary, our study helped to understand how electrically coupled retinal neurons are able to establish electrical synapses with different synaptic partners and how these synapses can be differentially modulated. It also suggested that gap junctions may also serve signal facilitation or amplification in some retinal neurons.
Publications
- (2019) Localization of Retinal Ca2+/Calmodulin-Dependent Kinase II-β (CaMKII-β) at Bipolar Cell Gap Junctions and Cross-Reactivity of a Monoclonal Anti-CaMKII-β Antibody With Connexin36. Frontiers in molecular neuroscience 12 206
Tetenborg, Stephan; Yadav, Shubhash Chandra; Brüggen, Bianca; Zoidl, Georg R.; Hormuzdi, Sheriar G.; Monyer, Hannah; van Woerden, Geeske M.; Janssen-Bienhold, Ulrike; Dedek, Karin
(See online at https://doi.org/10.3389/fnmol.2019.00206) - (2016) Connexin30.2: In Vitro Interaction with Connexin36 in HeLa Cells and Expression in AII Amacrine Cells and Intrinsically Photosensitive Ganglion Cells in the Mouse Retina. Front Mol Neurosci 9:36
Meyer A, Tetenborg S, Greb H, Segelken J, Dorgau B, Weiler R, Hormuzdi SG, Janssen- Bienhold U, Dedek K
(See online at https://doi.org/10.3389/fnmol.2016.00036) - (2016) Expression and Localization of Connexins in the Outer Retina of the Mouse. J Mol Neurosci 58(2):178-92
Bolte P, Herrling R, Dorgau B, Schultz K, Feigenspan A, Weiler R, Dedek K, Janssen- Bienhold U
(See online at https://doi.org/10.1007/s12031-015-0654-y) - (2017) Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36). Front Mol Neurosci 10: 425
Tetenborg S, Yadav SC, Hormuzdi SG, Monyer H, Janssen-Bienhold U, Dedek K
(See online at https://doi.org/10.3389/fnmol.2017.00425) - (2018) Phenotyping of Gap-Junctional Coupling. Methods Mol Biol 1753:249-259
Meyer A, Yadav SC, Dedek K
(See online at https://doi.org/10.1007/978-1-4939-7720-8_17) - (2019) Gap Junctions in A8 Amacrine Cells Are Made of Connexin36 but Are Differently Regulated than Gap Junctions in AII Amacrine Cells. Front Mol Neurosci 12:99
Yadav SC, Tetenborg S, Dedek K
(See online at https://doi.org/10.3389/fnmol.2019.00099)
