Connexin 36 gap junctions are essential for cone–mediated oscillatory potentials in the mouse electroretinogram (ERG)

Abstract

Abstract: : Purpose: Connexin36 (Cx36) forms gap junctions in the outer and inner retina, which are missing in the Cx36 knockout mouse. The purpose of this study was to analyze the impact of the lack of Cx36 on the function of the rod and the cone system separately by means of double mutant mice deficient of Cx36 plus either Rho (rod opsin knockout, cone specific) or Cnga3 (cone cyclic nucleotide–gated channel knock–out, rod specific). Methods: Double mutant mice were generated by cross–breeding Cx36–/– mice with either Rho–/– or Cnga3–/– animals. The resulting double knockouts (DKOs) in the F2 were identified by PCR. Mice were studied by scotopic and photopic electroretinography (ERG) using previously reported protocols (Seeliger et al., Nat Genet 2001; 29: 70–74). Results: Cx36–deficient mice had normal basal ERG amplitudes but obvious abnormalities in the oscillatory potentials (OPs), a set of higher frequency wavelets riding on the basal response. In the dark adapted state, the OPs were about normal up to intermediate stimulus intensity levels, but then rapidly decreased with intensity and were completely absent at the highest stimulus strengths around 10 cds/m². In photopic ERG, OPs were strongly reduced at all stimulus intensities. In the rod–specific DKO, the scotopic results were largely comparable to those in a single Cx36–/– mouse except for the missing cone contribution at higher intensities, and the photopic recording was flat. In the cone–specific DKO, both scotopic and photopic records had absent or very small OPs. Conclusions: This study provides evidence that functional connexin 36 gap junctions are essential for cone–mediated oscillatory potentials in the mouse electroretinogram. The reduction in scotopic OPs in response to very strong stimuli may be due to the lack of cone OPs or caused by an additional effect on the rod system.

Keywords: gap junctions/coupling • electroretinography: non–clinical • retinal connections, networks, circuitry