A key objective of this work is to clarify the extent to which hyperpolarizing bipolar and/or horizontal cells (HBC/HzCs) contribute to the electroretinogram (ERG), by performing intraretinal recordings and by pharmacological dissection of ERG responses. The ERG is an important tool to evaluate photoreceptor function noninvasively in animals and human patients. New analytical models for the human a-wave by Hood & Birch and by Bretton & Pugh will further increase its power. Although the a-wave commonly is thought to derive from photoreceptors rather directly, we have performed a pharmacological analysis of the monkey light-adapted ERG and have found that hyperpolarizing retinal second-order neurons appear to contribute a negative potential to the photopic a- and b-waves. HBC/HzC activity appears to shape the photopic b-wave and control its amplitude. Further, the negative wave from HBC/HzCs is sufficiently fast to add to the """"""""true"""""""" cone a-wave, particularity for stimulus conditions that are used clinically in human ERG diagnosis. If the existance of a proximal a-wave can be substantiated by further studies, this would change current clinical ERG analysis substantially. Finally, preliminary studies with glutamate analogs called into question the conventional idea that flicker ERG, measured at the cornea, reflects cone activity directly, since 30Hz flicker response all but disappeared after intravitreal injection of aspartate. Studies are proposed to learn the extent to which flicker ERG originates post-synaptic to photoreceptors. The ERG will be studied. Information developed should have direct application to the use of ERG in diagnosing human retinal dysfunction. The rodent ERG had gained additional importance as a non-invasive tool for the evaluating of naturally occurring and transgenetically engineered models of retinal dystrophies. Lastly, recording from these two species may provide insight into the biology underlying Granit's E-type and I- type ERG designations.
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