The light response of ON bipolar neurons requires G alpha(o)

ON bipolar neurons in retina detect the glutamate released by rods and cone s via metabotropic glutamate receptor 6 (mGluR6), whose cascade is unknown. The trimeric G-protein G(o) might mediate this cascade because it colocali zes with mGluR6. To test this, we studied the retina in mice negative for t he a subunit of G(o) (G alpha (o) -/-). Retinal layering, key cell types, s ynaptic structure, and mGluR6 expression were all normal, as was the a-wave of the electroretinogram, which represents the rod and cone photocurrents. However, the b-wave of the electroretinogram, both rod- and cone-driven co mponents, was entirely missing. Because the b-wave represents the massed re sponse of ON bipolar cells, its loss in the G alpha (o) null mouse establis hes that the light response of the ON bipolar cell requires G(o). This repr esents the first function to be defined in vivo for the alpha subunit of th e most abundant G-protein of the brain.