Pharmacological analysis of the rat cone electroretinogram

The electroretinogram (ERG) of the cone system provides a useful noninvasive measure of the activity of the cone pathway. Despite a wide application of the cone ERG in the study of rodent models of human hereditary retinal disease, the cellular origins of the rat cone ERG have not been well defined. Here, we address this issue using a pharmacological approach that has been used previously to derive ERG response components. Agents that impair synaptic transmission at well-defined retinal loci were dissolved in saline and injected into the vitreous of adult Sprague-Dawley rats anesthetized with ketamine/xylazine, and cone ERGs were recorded approximately 2 h later. Analysis of the resulting waveforms indicated that the rat cone ERG includes a relatively small-amplitude component of negative polarity that is derived from the activity of cone photoreceptors, and perhaps retinal glial (Müller) cells. The cone depolarizing bipolar cell pathway contributes a positive potential of large amplitude to the rat cone ERG. In comparison, the contribution of hyperpolarizing bipolar cells is of negative polarity and of much smaller amplitude. The inner retina contributes a negative wave upon which higher frequency oscillations are superimposed. These results provide a foundation for interpreting changes in the waveform of the rat cone ERG that may be observed following genetic alteration or other experimental treatment.