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.