Intrinsic cone adaptation modulates feedback efficiency from horizontal cells to cones

Processing of visual stimuli by the retina changes strongly during light/da rk adaptation. These changes are due to both local photoreceptor-based proc esses and to changes in the retinal network. The feedback pathway fron hori zontal cells to cones is known to be one of the pathway that is modulated s trongly during adaptation. Although this phenomenon is well described, the mechanism for this change is poorly characterized. The aim of this paper is to describe the mechanism for the increase in efficiency of the feedback s ynapse from horizontal cells to cones. We show that a train of flashes carl increase the feedback response from the horizontal cells, as measured in t he cones, up to threefold. This: process has a time constant of similar to 3 s and call be attributed to processes intrinsic to the cones. It does not require dopamine, is not the result of changes in the kinetics of thr cone light response and is riot due to changes in horizontal cells themselves. During a flash train, cones adapt to the mean light intensity, resulting in a slight (4 mV) depolarization of the cones. The time constant of this dep olarization is similar to 3 s. We will show that at this depolarized membra ne potential, a light-induced change of the cone membrane potential induces a larger change in the calcium current than ill the unadapted condition. F urthermore, we will show that negative feedback from horizontal cells to co nes can modulate the calcium current more efficiently at this depolarized c one membrane potential. The change in horizontal cell response properties d uring the train of flashes can be fully attributed to these changes in the synaptic efficiency. Since feedback has major consequences for the dynamic, spatial, and spectral processing, the described mechanism might be very im portant to optimize the retina for ambient light conditions.