July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Horizontal Cell Specific Dopamine Receptor Knock Out Causes ON vs OFF-pathway Specific Dysfunction in Spatial Tuning and Light Adaptation in the Retina
Author Affiliations & Notes
  • David Sprinzen
    Neuroscience, Vanderbilt, Nashville, Tennessee, United States
  • Douglas McMahon
    Neuroscience, Vanderbilt, Nashville, Tennessee, United States
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 607. doi:
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      David Sprinzen, Douglas McMahon; Horizontal Cell Specific Dopamine Receptor Knock Out Causes ON vs OFF-pathway Specific Dysfunction in Spatial Tuning and Light Adaptation in the Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):607.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The role of dopamine within the mammalian retina is to act as a circadian-regulated neuromodulator to reconfigure retinal processing during light adaptation; however, it is still unknown how dopamine modifies different cell types in the retina to achieve this. Horizontal cells, in particular, are thought to be an important location for dopaminergic modulation as dopamine causes significant changes to excitability, synaptic strength, and coupling of horizontal cells. Here, we used multi-electrode array (MEA) recordings of D1r knock out mice (D1rKO) and horizontal cell specific D1r knock out mice (HC-D1rKO) to elucidate the role of dopamine receptor activity on retinal processing. By comparing the deficits found in the D1rKOs and the HC-D1rKOs we can further our understanding of how dopamine is utilized in the retina and the role that distinct cell classes play in the process of dopamine mediated light adaptation.

Methods : Cell-specific deletion of D1R in the retina was obtained with mouse embryonic stem cells harboring a Drd1tma1(KOMP)Wtsi reporter-tagged insertion. MEA recordings were obtained from mice with germ-line deletion of D1r (n=5), post-flip conditional D1r crossed with the cx57-iCre horizontal cell specific Cre (n=6) and cre negative controls (n=6). Retinal ganglion cell activity of isolated mouse retinas was quantified before and after application of dopamine while applying various stimuli patterns of white noise, contrast gratings, and random square.

Results : Preliminary findings show that HC-D1rKO mice have deficits in the center size and dopamine mediated attenuation of ON cell type receptive fields, however OFF cell types primarily show changes in their receptive field surround size and properties.

Conclusions : Light adaptation is a complex process involving various changes across many cell types in the retina and thus study of how dopamine is utilized by the retinal circuit can inform our understanding of how the retina adjusts its processing to fit the light environment. Here we have shown that the effects of dopamine receptor knock out are asymmetrical on the circuits for ON vs OFF signal processing in the retina, suggesting that light adaptation, and specifically the role of horizontal cells, may differentially control the primary visual signaling pathways.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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