Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes. (February 2016)

• Record Type: Journal Article
• Authors: Cowan, Cameron S.; Abd-El-Barr, Muhammad; van der Heijden, Meike; Lo, Eric M.; Paul, David; Bramblett, Debra E.; Lem, Janis; Simons, David L.; Wu, Samuel M.
• Is Part Of: Vision research. Volume 119(2016)
• Page Start: 99
• Page End: 109
• Publication Date: 2016-02
• Subjects: RGCs retinal ganglion cells -- OKRs optokinetic reflexes -- Trα transducin-α -- Cx36 connexin 36 -- Bhlhb4 basic helix-loop-helix beta 4 -- AIIACs AII amacrine cells -- MEA multi-electrode array; Rod pathway -- Retinal ganglion cell -- Optokinetic reflex -- Rod information convergence and segregation -- Mouse retina -- Night vision; Vision -- Periodicals; 573.88
• DOI: 10.1016/j.visres.2015.11.006
• Languages: English
• ISSNs: 0042-6989

Abstract

Highlights: The sample of 900 retinal ganglion cells had evenly distributed light sensitivities. A connexin-36 independent rod pathway drives ON responses in retinal ganglion cells. Connexin-36 independent ON responses are dependent on mGluR6. Optokinetic reflexes of connexin-36 knockout mice persist in scotopic conditions. Altering rod pathway circuitry shifts mesopic optokinetic reflex tuning. Abstract: Rod pathways are a parallel set of synaptic connections which enable night vision by relaying and processing rod photoreceptor light responses. We use dim light stimuli to isolate rod pathway contributions to downstream light responses then characterize these contributions in knockout mice lacking rod transducin-α ( Trα ), or certain pathway components associated with subsets of rod pathways. These comparisons reveal that rod pathway driven light sensitivity in retinal ganglion cells (RGCs) is entirely dependent on Trα, but partially independent of connexin 36 ( Cx36 ) and rod bipolar cells. Pharmacological experiments show that rod pathway-driven and Cx36 -independent RGC ON responses are also metabotropic glutamate receptor 6-dependent. To validate the RGC findings in awake, behaving animals we measured optokinetic reflexes (OKRs), which are sensitive to changes in ON pathways. Scotopic OKR contrast sensitivity was lost in Trα −/− mice, but indistinguishable from controls in Cx36 −/− and rod bipolar cell knockout mice. Mesopic OKRs were also altered in mutant mice: Trα −/− mice had decreased spatial acuity, rod BC knockouts had decreased sensitivity, and Cx36 −/− mice had increased sensitivity. These results provide compelling evidence against the complete Cx36 or rod BC dependence of night vision's ON component. Further, the findings suggest the parallel nature of rod pathways provides considerable redundancy to scotopic light sensitivity but distinct contributions to mesopic responses through complicated interactions with cone pathways.