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On-Bipolar Cell Pathway, Motion Detection and Eye Movement Control

The photoreceptor /ON-bipolar cell synapse is a sign inverting metabotropic glutamatergic synapse. The components of the signaling cascade involved is driven by the metabotropic glutamate receptor are largely unresolved. Together with our collaborators Gregg (USA) and Peachey (NSA), we have found new proteins involved in this cascade: NYX, TRPM1 and GPR179. TRPM1 is the ion channel mediating the BC response.

Mixed input biolar cell filled with Lucifer Yellow (yellow). The green label is staingen with an antibody against PKC
Mixed input biolar cell filled with Lucifer Yellow (yellow). The green label is staingen with an antibody against PKC

The discovery of GRP179 is highly relevant since this might be the first example where two different G-protein coupled receptors (GMR6 and GPR179) form one functional complex. In collaboration with Bergen (NIN) and the foundation for the blind: Bartiméus, we were able to show that mutations in these genes lead to congenital stationary night blindness (CSNB) in humans. The availability of CSNB patients and mice- and zebrafish strains carrying mutations for these genes, offers an excellent opportunity to study the role of the ON-pathway in vision as a whole. For instance, we found that young children with mutations in proteins (NYX, TRPM1 or GRP179) in the rod to ON-bipolar cell synapse have a peculiar form of nystagmus.

Signaling cascade of ON-bipolar cells.
Signaling cascade of ON-bipolar cells.

We will continue our studies on the signaling cascade of the ON-bipolar cells and its relation to CNSB. We will extend our studies on the functional role of ON-bipolar cells in motion-detection and eye-movement control. Nystagmus is a ‘to and fro’ movement of the eyes with a slow phase and fast return phase. We will study how some forms of nystagmus may result from the interaction of malfunctioning ON-bipolar cells with the accessory optic system , the inferior olive and/or the cerebellum. We will focus on the properties of retinal directional selective ganglion cells in mice with and without mutated ON-bipolar cells. Overall these research lines will address the importance of retinal motion detection for higher visual processing and perception.