Concepts:

• vision science
• rod bipolar cells
• light adaptation
• electrophysiology
• statistical modeling
• metabotropic glutamate signaling

Source

Abstract:

Purpose

Mammalian rod bipolar cells desensitize with increases in mean luminance. This process of light adaptation reflects the sum of presynaptic gain changes in rods and postsynaptic changes in the mGluR6 signaling cascade. Here we dissect these contributions and study their underlying mechanism by measuring the properties of light-evoked signals in both rods and rod bipolar cells using patch electrodes.

Methods

Whole-cell voltage clamp recordings were made from rod photoreceptors and rod bipolar cells in dark-adapted mouse retinal slices. Light-evoked responses were recorded for a series of flashes in darkness and during the presentation of background light up to 400 Rh* (activated rhodopsins) rod^-1 sec^-1. A Hill equation with three free parameters was fit to the rod bipolar cell response-intensity relationship - including the maximum photocurrent (Rmax), the half-maximal flash strength (k), and the extent of nonlinearity in response amplitude as a function of flash strength (n).

Results

Rod photoreceptors exhibited a 2-fold loss of sensitivity at light intensities that cause ~50 Rh* sec^-1. Downstream rod bipolar cells exhibit a more complicated sensitivity change. In dim backgrounds, n was reduced from a value of 1.6 in darkness to 1.0 by ~10 Rh* rod^-1 sec^-1. At brighter light intensities, k began to shift, reflecting the decline in rod sensitivity. Rmax was also reduced by up to 60% at the brightest backgrounds tested. Dialysis of 10mM BAPTA during recordings, or holding the membrane potential at +50mV, reduced this modulation. Nonstationary noise analysis of the falling phase of light-evoked responses elicited in darkness and in background light reveal that the reduction in Rmax does not arise from a reduced TRPM1 single-channel current. Instead, it must result from a reduction in the coupling between the mGluR6 receptors and TRPM1 channels.

Conclusions

Measurements in mouse rod bipolar cells reveal that the loss in sensitivity as a function of background light is a combination of the loss in sensitivity due to rod phototransduction, along with mechanisms intrinsic to the rod bipolar cell dendrites. These collectively allow rod bipolar cells to respond robustly to single photon absorptions in a minority of the rods, while continuing the signal at brighter lights that also cause rod adaptation.

This is a 2021 ARVO Annual Meeting abstract.