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Morven Alison Cameron, Victor Perez Fernandez, Nina Milosavljevic, John W Morley; Rod input drives, and supresses, dopamine release in the mouse retina.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3099.
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We have previously shown, using a variety of transgenic and degenerate mouse models that rod input is necessary for light-induced dopamine release in the mouse retina. The purpose of this study was to further describe the circuits involved in the transfer of this information to dopaminergic amacrine cells and the subsequent release of dopamine at different light intensities.
We used UHPLC-MS/MS analysis to quantify dopamine release, and immunohistochemistry to assess activation of dopaminergic amacrine cells in the mouse retina both in vivo and in vitro. The three classes of photoreceptors were activated either by various intensities and wavelengths of light, or chemically via the expression of hM3Dq receptors in ipRGCs (DREADDs). Animals were subjected to light intensities ranging from around rod threshold (7.1 log rod photons cm-2 s-1) to high photopic (15.8 log rod photons cm-2 s-1).
We find that rods suppress the release of dopamine turnover at dim light intensities (10.2 log rod photons cm-2 s-1) when compared to near-infrared illumination (7.1 log rod photons cm-2 s-1), and drive dopamine turnover in the high photopic range (≥14.3 log rod photons cm-2 s-1). In agreement with previous work on retinally degenerate (rd/rd) mice lacking rods and cones, we find no c-fos activation of dopaminergic amacrine cells when ipRGCs are activated via clozapine-N-oxide in animals that express hM3Dq receptors in ipRGCs. Furthermore, we assessed light-induced dopamine turnover in rd/rd mice before the degeneration of cones (P18) and found no significant increase compared to wild-types which show robust light-induced dopamine release at this age.
We conclude that dopamine release is signifcantly increased under either very dim light around threshold, or very bright light with release suppressed at irradiances between these extremes. Furthermore, rod input is essential to define this release profile over 8 log units of light intensity. While cone and/or ipRGC input may be important in modulating this response, neither are necessary or sufficient to drive dopamine release.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure: Electroretinogram (ERG) b-wave amplitude (A) compared to dopamine turnover (DOPAC:DA ratio) in wild-type mice as a function of log effective rod photons cm-2 s-1. All light stimuli white light with the exception of the lowest two irradiances in B.
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