Abstract
Abstract: :
In human psychophysics, it is well known that after a brilliant desensitizing flash, cone flicker sensitivity first increases but then, paradoxically, decreases with a time course paralleling rod dark adaptation. This interaction between rods and cones is called suppressive rod-cone interaction (SRCI). Analogous physiological effects involving rod and cone signals occur in horizontal cells (HCs) and bipolar cells. For example, in cat, dim backgrounds enhance small-spot flicker responses of HCs. This is called background-induced flicker enhancement. In 1990, Nelson et al (J. Neurophysiol. 64: 326-339) proposed a biophysical model to explain the enhancement effect. Their hypothesis is that depolarized HC dendritic terminals, in a feedback effect, decrease the entry of calcium into the cone terminal. Hyperpolarization of the HC with background illumination reduces this effect, allowing calcium to enter the terminal, stimulating transmitter release by the cone presynaptic apparatus, hence increasing synaptic gain. Purpose: The purpose of this study is to test the validity of this biophysical model by checking if its predictions are consistent with data from flicker enhancement experiments. Methods: A computational model incorporating the details of the proposed biophysical mechanism is formulated and then solved using numerical methods. Simulations for a two-cell feedback model are compared to experimental data for the enhancement effect and to data exhibiting frequency and phase-shift properties (Pflug et al, J. Neurophysiol. 64: 313-325, 1990). The model is then extended to the entire HC syncytium to explore spatial properties. This spatial model includes the effects of thousands of HC dendritic spines. Results: The two-cell feedback model displays enhancement, frequency and phase shift effects as observed experimentally. The simulations demonstrate that the enhancement effect, frequency and phase-shift properties are independent of other HC waveform elements such as ‘sag', a slow depolarizing effect seen during light stimulation. The spatial extension of the model captures the reduction in enhancement effect with increasing test-slit widths. Conclusion: The predictions of the biophysical model are consistent with data from flicker enhancement experiments, and suggest that a simple model in which HC dendrites regulate calcium entry into cone synapses can account for the spatio-temporal properties of background-induced enhancement effects related to SRCI. ‘Sag', another HC response element, might be modeled by the addition of H currents.
Keywords: retina: distal(photoreceptors, horizontal cell • computational modeling • synapse