HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure.

Vithiyanjali Sothilingam,Stylianos Michalakis,Marina Garcia Garrido,Naoyuki Tanimoto,Martin Biel,Mathias W Seeliger

doi:10.1371/journal.pone.0147728

Abstract

PurposeVision originates in rods and cones at the outer retina. Already at these early stages, diverse processing schemes shape and enhance image information to permit perception over a wide range of lighting conditions. In this work, we address the role of hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1) in rod photoreceptors for the enhancement of rod system responsivity under conditions of light exposure.MethodsTo isolate HCN1 channel actions in rod system responses, we generated double mutant mice by crossbreeding Hcn1-/- mice with Cnga3-/- mice in which cones are non-functional. Retinal function in the resulting Hcn1-/- Cnga3-/- animals was followed by means of electroretinography (ERG) up to the age of four month. Retinal imaging via scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) was also performed to exclude potential morphological alterations.ResultsThis study on Hcn1-/- Cnga3-/- mutant mice complements our previous work on HCN1 channel function in the retina. We show here in a functional rod-only setting that rod responses following bright light exposure terminate without the counteraction of HCN channels much later than normal. The resulting sustained signal elevation does saturate the retinal network due to an intensity-dependent reduction in the dynamic range. In addition, the lack of rapid adaptational feedback modulation of rod photoreceptor output via HCN1 in this double mutant limits the ability to follow repetitive (flicker) stimuli, particularly under mesopic conditions.ConclusionsThis work corroborates the hypothesis that, in the absence of HCN1-mediated feedback, the amplitude of rod signals remains at high levels for a prolonged period of time, leading to saturation of the retinal pathways. Our results demonstrate the importance of HCN1 channels for regular vision.

Highlights

The retina is able to respond to a wide range of light stimuli by the use of the two photoreceptor subtypes, rods and cones, whose signals converge at different sites in the retina
We show here in a functional rod-only setting that rod responses following bright light exposure terminate without the counteraction of HCN channels much later than normal
This work corroborates the hypothesis that, in the absence of hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1)-mediated feedback, the amplitude of rod signals remains at high levels for a prolonged period of time, leading to saturation of the retinal pathways

Summary

Introduction

The retina is able to respond to a wide range of light stimuli by the use of the two photoreceptor subtypes, rods and cones, whose signals converge at different sites in the retina. The wide response range is implemented at the level of photoreceptors, and downstream via the use of parallel, independent pathways and intensity-dependent convergence of signals at each stage of retinal processing [3,4,5]. The primary rod pathway operates at dim light conditions and connects rods via rod bipolar cells to AII amacrine cells and eventually the cone ON pathway. Horizontal connections at each level of signal processing (e.g. via gap junctions) are important for several aspects of vision [10]

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