1 A computational study of background-induced flicker enhancement and feedback mechanisms in vertebrate outer retina : temporal properties

In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback mechanism. This feedback has a number of important physiological consequences. One is called backgroundinduced flicker enhancement in which the onset of dim background enhances the center flicker response of horizontal cells. The underlying mechanism for the feedback is unclear but competing hypotheses have been proposed. One is the GABA hypothesis, which states that the inhibitory neurotransmitter GABA, released from horizontal cells, mediates the feedback by blocking calcium channels. Another is the ephaptic hypothesis, which contends that calcium entry is regulated by changes in the electrical potential within the intersynaptic space between cones and horizontal cells. In this study, a continuum spine model of the cone-horizontal cell synaptic circuitry is formulated. This model, a partial differential equation system, incorporates both the GABA and ephaptic feedback mechanisms. Simulation results, in comparison with experiments, indicate that the ephaptic mechanism is necessary in order for the model to capture the major temporal dynamics of background-induced flicker enhancement. In addition, the results indicate that the GABA mechanism may play a secondary modulation role. Simulations that included both mechanisms best fit (qualitatively) the cat enhancement data, and provided valuable insights into interpreting the dynamics of calcium activation in feedback experiments on goldfish retina.