Phosducin Regulates Transmission at the Photoreceptor-To-ON Bipolar Cell Synapse

Abstract

Purpose: : The vertebrate retina has a remarkable ability to adapt the sensitivity of its light responses to dramatic changes in the ambient illumination which occur during the normal diurnal cycle. Dark and light adaptation take place both in the biochemical phototransduction cascade of rods and cones and at essentially every stage of the retinal circuitry. One aspect of light adaptation is the regulation of light-sensitivity of rodON-bipolar cells functioning immediately downstream from photoreceptors. Rod ON-bipolar cells are very sensitive to light under dark-adapted conditions and can be saturated by light at least 10-fold dimmer than that required to saturate rods. Persistent illumination causes rod ON-bipolar cell desensitization, which results in extension of their operating range. The molecular mechanisms underlying this process are poorly understood. Our aim was to identify a potential mechanism that pre-synaptically regulates photoreceptor-to-ON bipolar cell synaptic transmission.

Methods: : We conducted electroretinographic recordings from dark- and light-adapted mice lacking the abundant photoreceptor protein, phosducin. For control experiments we transgenically expressed phosducin in phosducin knockout rods. The morphology of the rod synapse in phosducin knockout mice was studied with electron microscopy.

Results: : We found that the ON-bipolar cell responses in phosducin knockout animals have a reduced light-sensitivity in the dark-adapted state. This effect was observed in both rod- and cone-driven pathways, with the latter affected to a larger degree. The rod-specific phenotype was rescued by transgenic expression of phosducin in rods of phosducin knockout mice showing that the underlying mechanism is confined to photoreceptors.

Conclusions: : Our data indicate that at least one major regulatory component responsible for setting the sensitivity of signal transmission between photoreceptors and ON-bipolar cells has a pre-synaptic origin.

Keywords: photoreceptors • synapse • electroretinography: non-clinical