Mind the gap (junction)

In the retina, the role of structures allowing two types of nerve cells to exchange electrical signals is coming to light.

3D reconstruction of two adjacent cone terminals, showing many fine processes which reach out to nearby rods. Image credit: Ishibashi et al. (CC BY 4.0)

Neurons can talk to each other in two ways: they can send chemical messengers across specialized junctions between two cells, or they can directly pass electrical signals to one another. This latter process is made possible by gap junctions, a system of channel-like structures which connect neighbouring cells and let ions move between them. In most neurons, gap junction channels are made from a specialized protein called connexin 36. Gap junctions are small, difficult to observe, and therefore often ignored by researchers studying neural circuits.

In response, Ishibashi et al. focused on nerve cells in the mouse retina, in particular the cones (which detect color during the day) and the rods (which are essential for night vision). Gap junctions between rods and cones allow them to communicate; for example, they enable rod signals to directly activate cones. This provides an alternative route for rod signaling known as the ‘secondary rod pathway’, which seems to be open at night and switches to closed around dawn.

Both rods and cones only produce connexin 36, so Ishibashi et al. labeled these proteins with fluorescent tags to pinpoint gap junctions. This showed that each cone makes around 50 gap junctions with nearby rods; however, gap junctions were not detected between cells of the same type.

In addition, 3D reconstruction helped to establish the length of each gap junction. Further experiments showed that a typical rod was connected to a cone by about 80 connexin 36 channels. Finally, calculations revealed that the gap junction channels would all need to open to account for the level of electrical activity required for the secondary rod pathway. This suggests that gap junctions may be much more active and important than previously thought.

The work by Ishibashi et al. provides a new understanding of the number, size and activity of gap junctions in the retina, potentially paving the way to prevent diseases where light-sensing cells degenerate and cause blindness.