title: Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9.
abstract: The temporal resolution of scotopic vision is thought to be constrained by the signaling kinetics of retinal rods, which use a highly amplified G-protein cascade to transduce absorbed photons into changes in membrane potential. Much is known about the biochemical mechanisms that determine the kinetics of rod responses ex vivo, but the rate-limiting mechanisms in vivo are unknown. Using paired flash electroretinograms with improved signal-to-noise, we have recorded the amplitude and kinetics of rod responses to a wide range of flash strengths from living mice. Bright rod responses in vivo recovered nearly twice as fast as all previous recordings, although the kinetic consequences of genetic perturbations previously studied ex vivo were qualitatively similar. In vivo, the dominant time constant of recovery from bright flashes was dramatically reduced by overexpression of the RGS9 complex, revealing G-protein deactivation to be rate limiting for recovery. However, unlike previous ex vivo recordings, dim flash responses in vivo were relatively unaffected by RGS9 overexpression, suggesting that other mechanisms, such as calcium feedback dynamics that are strongly regulated by the restricted subretinal microenvironment, act to determine rod dim flash kinetics. To assess the consequences for scotopic vision, we used a nocturnal wheel-running assay to measure the ability of wild-type and RGS9-overexpressing mice to detect dim flickering stimuli and found no improvement when rod recovery was speeded by RGS9 overexpression. These results are important for understanding retinal circuitry, in particular as modeled in the large literature that addresses the relationship between the kinetics and sensitivity of retinal responses and visual perception.
authors.affiliation: Center for Neuroscience, University of California, Davis, Davis, CA 95618.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Peinado Allina
authors.affiliation: Center for Neuroscience, University of California, Davis, Davis, CA 95618.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fortenbach
authors.affiliation: Department of Psychology, Northeastern University, Boston, MA 02115.
authors.forename: Franklin
authors.identifier: http://orcid.org/0000-0002-8240-8389
authors.initials: F
authors.lastname: Naarendorp
authors.affiliation: Center for Neuroscience, University of California, Davis, Davis, CA 95618.
authors.forename: Owen P
authors.initials: OP
authors.lastname: Gross
authors.affiliation: Center for Neuroscience, University of California, Davis, Davis, CA 95618.|Department of Ophthalmology and Vision Science, University of California, Davis, Davis, CA 95618.|Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA 95618.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Pugh
authors.affiliation: Center for Neuroscience, University of California, Davis, Davis, CA 95618 meburns@ucdavis.edu.|Department of Ophthalmology and Vision Science, University of California, Davis, Davis, CA 95618.|Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA 95618.
authors.forename: Marie E
authors.identifier: http://orcid.org/0000-0003-3766-2780
authors.initials: ME
authors.lastname: Burns
mesh_terms: D000818:Animals; D055537:Light Signal Transduction; D051379:Mice; D008810:Mice, Inbred C57BL; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D020710:RGS Proteins; C116925:regulator of g-protein signaling 9