title: Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes.
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.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States; Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States. Electronic address: Cameron.Cowan@gmail.com.
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Cowan
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abd-El-Barr
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Meike
authors.initials: M
authors.lastname: van der Heijden
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Lo
authors.affiliation: Department of Neurobiology, Harvard University, Boston, MA, United States.
authors.forename: David
authors.initials: D
authors.lastname: Paul
authors.affiliation: Department of Medical Education, Paul L. Foster School of Medicine-TTUHSC, El Paso, TX, United States.
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bramblett
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, United States.
authors.forename: Janis
authors.initials: J
authors.lastname: Lem
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Simons
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States; Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Wu
mesh_terms: D000818:Animals; D017630:Connexins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D017120:Nystagmus, Optokinetic / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D051245:Retinal Bipolar Cells / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology*; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D000097004:Gap Junction delta-2 Protein
keywords: Mouse retina; Night vision; Optokinetic reflex; Retinal ganglion cell; Rod information convergence and segregation; Rod pathway