The Sensitivity to Light Decrement Controls Rod Response to Flickering Light

Abstract

Purpose : The recovery kinetics of rod photoreceptor response controls rod response to sinusoidal flicker and consequently sets mouse behavioral flicker sensitivity (temporal contrast sensitivity, TCS) at mesopic lights (Umino Y et al., 2019). The purpose of this work is to study the mechanism underlying the control of rod flicker response by rod recovery kinetics. We hypothesize that faster rod recovery kinetics would enhance rod sensitivity to light decrement, leading to increased rod flicker response.

Methods : Rod flicker response was recorded by trans-retinal ERG in WT and a transgenic line (R9OE) over-expressing R9AP that has faster rod recovery kinetics due to increased G_tα*-E* inactivation. Retinas were perfused with Ames medium supplemented with DL-AP4 (50 μM), CNQX (20 μM) and BaCl2 (100 μM) to isolate photoreceptor response. Because the sinusoidal stimuli does not permit separation of response to light increments and decrements, we utilized square wave flicker of 75% contrast of 0.5 Hz at backgrounds 10–3200R*/rod/s. All comparisons were done at equivalent suppression of circulating current to match the effect of calcium feedback on rod response.

Results : We used brief flashes of various intensities to measure the dim flash sensitivity and the EC50 at different backgrounds to represent rod sensitivity to light increment. WT and R9OE mice display similar flash sensitivity and EC50. We also found that WT and R9OE mice have similar ON responses to square flicker at all backgrounds. By contrast, WT and R9OE mice have similar OFF responses to square flicker which increase with background until 80 R*/rod/s, above which they diverge. WT mice response remains constant while, R9OE mice response keeps increasing, peaking at 800 R*/rod/s and then decreasing. Thus, R9OE mice exhibit larger OFF responses at 80-3200 R*/rod/s, consistent with behavioral flicker sensitivity. We also used 1.5-second steps of various negative contrasts to acquire the contrast gain to light decrement. WT and R9OE mice have similar contrast gain at <80 R*/rod/s. While, R9OE mice display higher contrast gain than WT mice at 80-3200 R*/rod/s.

Conclusions : At mesopic light, the rate of G_tα*-E* inactivation in rod phototransduction cascade sets rod sensitivity to light decrement. Thus, the rod sensitivity to light decrement, not increment, controls rod response and behavioral sensitivity to flicker.

This is a 2021 ARVO Annual Meeting abstract.