Abstract
Purpose :
We have previously shown that dopamine turnover in the mouse retina is high-threshold, driven by rod photoreceptors and occurs within 30 sec of light onset. However, light-induced dopamine turnover shows a transient reduction approximately 5 min after light onset and then recovers to a maximum at 15 min. Here we present a mathematical model to describe the temporal properties of dopamine turnover in response to light.
Methods :
To estimate the dynamics of dopamine release in response to light, we developed a simplified model in Simulink (Matlab, The Mathworks). Independent model elements are described as transfer functions in the Laplace domain.
Results :
The simplest model that replicated the physiological data comprised a step in light input that elicited dopamine release low-pass filtered (τ = 20 s) minus a negative feedback component and a direct inhibitory component. The negative feedback is the effect of dopamine release itself on the amplitude of the light input low-passed (τ = 100 s) and delayed 60 s, which declines slowly over time (τ = 1000 s), possibly reflecting the effect of dopamine on retinal cell function/circuitry. The direct inhibitory component comes directly from the light input, however, while this direct inhibition is included in both the light and dark responses its impact is only clearly observable as a transient increase in dopamine release following transition to dark. This direct inhibitory component exactly matches the reduction in dopamine turnover we observe when dim light is applied to the retina.
Conclusions :
We conclude that the regulation of dopamine turnover in the mouse retina relies on a balance of excitatory and inhibitory inputs both driven by rod photoreceptors.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.