The prion protein is required for normal responses to light stimuli by photoreceptors and bipolar cells

The prion protein, PrP^C, is well known as an essential susceptibility factor for neurodegenerative prion diseases, yet its function in normal, healthy cells remains uncertain. A role in synaptic function has been proposed for PrP^C, supported by its cell surface expression in neurons and glia. Here, in mouse retina, we localized PrP^C to the junctions between photoreceptors and bipolar cells using synaptic proteins EAAT5, CtBP2, and PSD-95. PrP^C localized most densely with bipolar cell dendrites synapsing with cone photoreceptors. In two coisogenic mouse strains, deletion of the gene encoding PrP^C, Prnp, significantly altered the scotopic and/or photopic electroretinographic (ERG) responses of photoreceptors and bipolar cells. Cone-dominant pathways showed the most significant ERG changes. Retinal thickness, quantitated by high-resolution optical coherence tomography (OCT), and ribbon synapse morphology were not altered upon deletion of PrP^C, suggesting that the ERG changes were driven by functional rather than structural alterations.