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      Influence of Aging on the Retina and Visual Motion Processing for Optokinetic Responses in Mice

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          Abstract

          The decline in visual function due to normal aging impacts various aspects of our daily lives. Previous reports suggest that the aging retina exhibits mislocalization of photoreceptor terminals and reduced amplitudes of scotopic and photopic electroretinogram (ERG) responses in mice. These abnormalities are thought to contribute to age-related visual impairment; however, the extent to which visual function is impaired by aging at the organismal level is unclear. In the present study, we focus on the age-related changes of the optokinetic responses (OKRs) in visual processing. Moreover, we investigated the initial and late phases of the OKRs in young adult (2–3 months old) and aging mice (21–24 months old). The initial phase was evaluated by measuring the open-loop eye velocity of OKRs using sinusoidal grating patterns of various spatial frequencies (SFs) and moving at various temporal frequencies (TFs) for 0.5 s. The aging mice exhibited initial OKRs with a spatiotemporal frequency tuning that was slightly different from those in young adult mice. The late-phase OKRs were investigated by measuring the slow-phase velocity of the optokinetic nystagmus evoked by sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that optimal SF and TF in the normal aging mice are both reduced compared with those in young adult mice. In addition, we measured the OKRs of 4.1G-null ( 4.1G –/–) mice, in which mislocalization of photoreceptor terminals is observed even at the young adult stage. We found that the late phase OKR was significantly impaired in 4.1G / mice, which exhibit significantly reduced SF and TF compared with control mice. These OKR abnormalities observed in 4.1G / mice resemble the abnormalities found in normal aging mice. This finding suggests that these mice can be useful mouse models for studying the aging of the retinal tissue and declining visual function. Taken together, the current study demonstrates that normal aging deteriorates to visual motion processing for both the initial and late phases of OKRs. Moreover, it implies that the abnormalities of the visual function in the normal aging mice are at least partly due to mislocalization of photoreceptor synapses.

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          Most cited references87

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          The Psychophysics Toolbox.

          D Brainard (1997)
          The Psychophysics Toolbox is a software package that supports visual psychophysics. Its routines provide an interface between a high-level interpreted language (MATLAB on the Macintosh) and the video display hardware. A set of example programs is included with the Toolbox distribution.
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            Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections.

            The retina contains ganglion cells (RGCs) that respond selectively to objects moving in particular directions. Individual members of a group of ON-OFF direction-selective RGCs (ooDSGCs) detect stimuli moving in one of four directions: ventral, dorsal, nasal, or temporal. Despite this physiological diversity, little is known about subtype-specific differences in structure, molecular identity, and projections. To seek such differences, we characterized mouse transgenic lines that selectively mark ooDSGCs preferring ventral or nasal motion as well as a line that marks both ventral- and dorsal-preferring subsets. We then used the lines to identify cell surface molecules, including Cadherin 6, CollagenXXVα1, and Matrix metalloprotease 17, that are selectively expressed by distinct subsets of ooDSGCs. We also identify a neuropeptide, CART (cocaine- and amphetamine-regulated transcript), that distinguishes all ooDSGCs from other RGCs. Together, this panel of endogenous and transgenic markers distinguishes the four ooDSGC subsets. Patterns of molecular diversification occur before eye opening and are therefore experience independent. They may help to explain how the four subsets obtain distinct inputs. We also demonstrate differences among subsets in their dendritic patterns within the retina and their axonal projections to the brain. Differences in projections indicate that information about motion in different directions is sent to different destinations.
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              Direction selectivity in the retina: symmetry and asymmetry in structure and function.

              Visual information is processed in the retina to a remarkable degree before it is transmitted to higher visual centres. Several types of retinal ganglion cells (the output neurons of the retina) respond preferentially to image motion in a particular direction, and each type of direction-selective ganglion cell (DSGC) is comprised of multiple subtypes with different preferred directions. The direction selectivity of the cells is generated by diverse mechanisms operating within microcircuits that rely on independent neuronal processing in individual dendrites of both the DSGCs and the presynaptic neurons that innervate them.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                01 December 2020
                2020
                : 14
                : 586013
                Affiliations
                Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University , Osaka, Japan
                Author notes

                Edited by: Fumitaka Osakada, Nagoya University, Japan

                Reviewed by: Keisuke Yonehara, Aarhus University, Denmark; Takashi Kodama, Johns Hopkins University, United States

                *Correspondence: Takahisa Furukawa, takahisa.furukawa@ 123456protein.osaka-u.ac.jp

                These authors have contributed equally to this work

                This article was submitted to Perception Science, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2020.586013
                7736246
                33335469
                b8db6dbf-c3a4-4d16-9198-a7fa78cd64ae
                Copyright © 2020 Sugita, Yamamoto, Maeda and Furukawa.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 July 2020
                : 10 November 2020
                Page count
                Figures: 9, Tables: 0, Equations: 1, References: 87, Pages: 16, Words: 0
                Categories
                Neuroscience
                Original Research

                Neurosciences
                aging,retina,eye movement,optokinetic response,electroretinogram,visual function,photoreceptor cells,horizontal cells

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