Cx36-independent rod pathways mediate visual contrast sensitivity to high temporal frequencies

Abstract

Purpose : In the retina, rod signals are transmitted along multiple pathways, each connecting to underlying cone circuitry. Rod signals spread to cone pathways via Cx36 gap junction electrical synapses (Cx36-dependent rod pathways) as well as by direct chemical synapses from rods to cone bipolar cells (Cx36-independent rod pathways), with the contribution of the latter to visual function still unclear. Our goal is to dissect the contributions of Cx36-dependent and independent rod pathways to temporal contrast sensitivity (TCS).

Methods : We utilized transgenic mouse lines (3-6 months) to separate retinal pathways and used a novel operant behavior assay developed in our lab to measure the TCS of mice in response to full-field flicker applied over a wide range of temporal frequencies and background intensities. Immunohistochemical and electroretinogram (ERG) analyses were performed to assess retinal integrity. Statistical significance was tested by two-way ANOVA.

Results : Operant behavior results show that mice with non-functional cones (GNAT2^cpfl3) have normal TCS at low mesopic backgrounds (100R*/rod/s). At higher mesopic backgrounds (2000R*/rod/s), GNAT2^cpfl3 mice exhibited a significant reduction in sensitivity to low temporal frequencies (1.5-12 Hz) (n=5+/-SEM) while their sensitivity to high temporal frequencies (15-42 Hz) remained normal. TCS to high frequencies also remained normal in Cx36^-/-::GNAT2^cpfl3 double mutant mice with isolated Cx36-independent rod pathways (n=4+/-SEM) suggesting that Cx36-independent rod pathways function to relay fast temporal information at 2000R*/rod/s. Control studies show that TCS to high frequency flicker is negligible (n=5+/-SEM) when presented in high (8000R*/rod/s) background levels suggesting that the observed responses are driven largely by rods and not by remaining cone function in GNAT2^cpfl3 mice. ERG recordings indicate that the mouse lines used for these studies did not exhibit overt remodeling (n=9+/-SEM).

Conclusions : Our results suggest that, at high mesopic light levels (2000R*/rod/s): 1) Cone pathways contribute to the detection of low temporal frequency flicker; and 2) the poorly understood Cx36-independent rod pathways relay high temporal frequencies. Together, these data are consistent with the concept that rod pathways play a dynamic role in mammalian visual function.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.