Light inputs to dopaminergic amacrine cells of the mammalian retina

Abstract

Background: The retina responds to light over a wide range of operational conditions, surpassing 10 units in a logarithmic scale. Adaptation of the retina to the particular presenting light conditions relies considerably on modulation of retinal pathways by dopamine, which is released in response to light or circadian rhythms exclusively from dopaminergic amacrine cells. Rods, cones and intrinsically photoresponsive retinal ganglion cells (ipRGCs) have all been shown to input into dopaminergic amacrine cells. However, the pathways that these photoreceptors employ to ultimately trigger dopamine release in response to light remain unclear. Methods: Ultra-high performance liquid chromatography separation and tandem mass spectrometry detection was used to quantify dopamine, and its primary metabolite 3,4-dihidroxyphenylacetic acid (DOPAC). Retinal dopamine release was assessed under various conditions, in a variety of mouse models, using two complementary experimental designs: in vivo anaesthetised mice and ex vivo explanted retinae. Conclusions: This thesis provides novel evidence about dopamine dynamics in a variety of light conditions, transgenic mouse models and presence of pharmacological agents. Surprisingly, I found that rod input is both necessary and sufficient to evoke light-induced release dopamine across a wide range of light intensities, without quantifiable contribution from cones or ipRGCs, suggesting that electrophysiological inputs do not match dopamine release. Further, this data suggests that the main pathway that drives this increase in light-induced dopamine release at light intensities where rods should be saturated is the primary rod pathway (with smaller contributions from the secondary and tertiary pathways) and involves bleaching adaptation of rods.

Date of Award	2018
Original language	English