A cellular and molecular model of response kinetics and adaptation in primate cones and horizontal cells

A model for the sensitivity regulation in the primate outer retina is developed and validated using horizontal cell measurements from the literature. The main conclusion is that the phototransduction of the cones is the key factor regulating sensitivity. The model consists of a nonlinearity cascaded with three feedback control loops. The nonlinearity is caused by the hydrolysis of cGMP by activated phosphodiesterase. The first feedback loop is divisive, with calcium regulating the photocurrent in the cone outer segment. The second feedback loop is also divisive, with voltage-sensitive channels regulating the membrane voltage of the cone inner segment. The final feedback loop is subtractive, where the membrane voltage of the horizontal cell is subtracted from that of the cone before the cone drives the horizontal and bipolar cells. The model describes adequately the major characteristics of the horizontal cell responses to wide field, spectrally white stimuli. In particular, it shows (1) sensitivity and bandwidth control as a function of background intensity; (2) the major nonlinearities observed in the horizontal cells; and (3) the transition from linear responses toward contrast constancy (Weber's law) for background illuminances ranging from 1-1000 td.