Contribution of chemical and electrical transmission to the low delta-like intrinsic retinal oscillation in mice: A role for daylight-activated neuromodulators.

Basal electroretinogram (ERG) oscillations have shown predictive value for modifiable risk factors for type 2 diabetes. However, their origin remains unknown. Here, we seek to establish the pharmacological profile of the low delta-like (δ1) wave in the mouse because it shows light sensitivity in the form of a decreased peak frequency upon photopic exposure. Applying neuropharmacological drugs by intravitreal injection, we eliminated the δ1 wave using lidocaine or by blocking all chemical and electrical synapses. The δ1 wave was insensitive to the blockade of photoreceptor input, but was accelerated when all inhibitory or ionotropic inhibitory receptors in the retina were antagonized. The sole blockade of GABAA, GABAB, GABAC, and glycine receptors also accelerated the δ1 wave. In contrast, the gap junction blockade slowed the δ1 wave. Both GABAA receptors and gap junctions contribute to the light sensitivity of the δ1 wave. We further found that the day light-activated neuromodulators dopamine and nitric oxide donors mimicked the effect of photopic exposure on the δ1 wave. All drug effects were validated through light flash-evoked ERG responses. Our data indicate that the low δ-like intrinsic wave detected by the non-photic ERG arises from an inner retinal circuit regulated by inhibitory neurotransmission and nitric oxide/dopamine-sensitive gap junction-mediated communication.