Mouse photoreceptors are electrically coupled via gap junctions, but the relative importance of rod/rod, cone/cone, or rod/cone coupling is unknown. Furthermore, while connexin36 (Cx36) is expressed by cones, the identity of the rod connexin has been controversial. We report that FACS-sorted rods and cones both express Cx36 but no other connexins. We created rod- and cone-specific Cx36 knockout mice to dissect the photoreceptor network. In the wild type, Cx36 plaques at rod/cone contacts accounted for more than 95% of photoreceptor labeling and paired recordings showed the transjunctional conductance between rods and cones was ~300 pS. When Cx36 was eliminated on one side of the gap junction, in either conditional knockout, Cx36 labeling and rod/cone coupling were almost abolished. We could not detect direct rod/rod coupling, and cone/cone coupling was minor. Rod/cone coupling is so prevalent that indirect rod/cone/rod coupling via the network may account for previous reports of rod coupling.

Mammalian retinal circuits are broadly divided into rod and cone pathways, responsible for dark- and light-adapted vision, respectively. The classic rod pathway employs a single type of rod bipolar cell, which synapses with AII amacrine cells. AII amacrine cells then pass the signal to ON and OFF cone bipolar cells, respectively. Alternatively, rod signals may enter cones via gap junctions between rods and cones, and then pass from cones to cone bipolar cells. Thus, this second rod pathway does not utilize rod bipolar cells. Finally, in rodents, a third rod pathway, involving direct connections between rods and certain OFF cone bipolar cells, has been suggested. In this study, 56 OFF cone bipolar cells in the rabbit retina were dye-injected with Lucifer Yellow and their photoreceptor connections were examined by confocal microscopy in wholemount. The locations of rod and cone terminals were marked with antibodies to mGluR6 or synaptic proteins. Most OFF cone bipolar dendrites terminated at cone pedicles but some made potential contacts with rod spherules. The synaptic nature of these sites was confirmed by the presence of GluR2 receptors. All three OFF bipolar cell types had dendrites that terminated at rod spherules. However, approximately 80% of Ba2 and Ba3, but only 26% of Ba1 OFF cone bipolar cells made rod contacts. This variability suggests differential rod input to certain retinal pathways. In summary, we report anatomical evidence for direct connections between rods and OFF cone bipolar cells in a nonrodent mammal. Our data suggest that this alternative rod pathway may be a common feature of the mammalian retina.

No abstract

Gap junctions are abundant in the mammalian retina and many neuronal types form neural networks. Several different neuronal connexins have now been identified in the mammalian retina. Cx36 supports coupling in the AII amacrine cell network and is essential for processing rod signals. Cx36 is probably also responsible for photoreceptor coupling. Horizontal cells appear to be extensively coupled by either Cx50 or Cx57. These results indicate that multiple neuronal connexins are expressed in the mammalian retina and that different cell types express different connexins.