Rodent electroretinography: Methods for extraction and interpretation of rod and cone responses

The flash electroretinogram (ERG) represents a serial ensemble of neural responses that can be used to objectively evaluate retinal function on a layer-by-layer basis. In this review, the seminal concepts of Granit are developed within the modern context to demonstrate how the ERG waveform can be decomposed to isolate the activity of individual neural populations and their circuitry. The contribution of rods and cones to the ERG waveform can be precisely defined with simple methods that yield the veridical cone response, which allows identification of rod-isolated components. This knowledge will afford an enhanced capacity to understand retinal development and ageing as well as to interpret the effects of insult, genetic manipulation and disease processes on photoreceptor and neuron-specific components. This review integrates conclusions drawn from a large body of past work and presents new data that enables the provision of detailed methodology for ERG assessment in rodents. Emphasis is placed on protocols that allow efficient acquisition of useful information for the major ERG components with minimal complexity. In particular, specific guidelines for the isolation of rod and cone contributions from the full-field ERG in rodents are provided. This is complemented with detailed and novel methodology for determining parameters that describe individual neuronal generators of rod and cone responses. The effect of stimulus energy on the kinetics of ERG response recovery and photopigment bleaching and regeneration are also discussed. The guidelines presented here are applicable to a wide range of investigations of retinal disease in rodent models.