Abstract
Purpose:
Retinal dopamine is both light induced and circadian-regulated and is thought to reconfigure the retinal circuitry during light adaption. To study the role that dopamine plays in the retina we used a retina-specific tyrosine hydroxylase knockout (rTHKO) mouse - the rate-limiting enzyme in dopamine production. By quantifying changes in coding properties like sensitivity, threshold, and gain at different levels of background illumination we assessed how these properties adjust to light level and how loss of dopamine affects their adaptation.
Methods:
Retinal ganglion cell's (RGCs) activity of isolated mouse retinas was recorded using a multi-electrode array (MEA) while applying various stimuli patterns such as white noise, contrast gratings, marching square, and full field light pulse, at background illumination increasing from from 1 to 60 cd/m2. Mouse retinas were dissected in dim red light, placed ganglion cell side down on perforated MEAs, and perfused with oxygenated Ames’ Medium. RGC’s were classified into five classes: on-center sustained, on-center transient, off-center, on/off directionally selective, and on directionally selective. Over the course of the recording, the coding properties of signal to noise ratio, latency, duration, threshold, gain and sensitivity were assayed at each level of illuminance and compared between genotypes.
Results:
We found that most non-directionally selective RGCs in rTHKO retinas exhibit an increase in noise when light adapted, an increase in response latency of around 20 ms, and various deficits in the coding efficacy that become more pronounced with increasing light level. Interestingly, no deficits were found with directionally selective cells. To verify that these deficits are ongoing and not developmental, we showed they could be rescued with a dopamine receptor agonist cocktail.
Conclusions:
Light adaptation is one of the most complex examples of plasticity within the visual system. By quantifying many of the response characteristics of retinal ganglion cells at multiple levels of illumination, we have provided insight into how the retina optimally encodes the visual signal as well as how this process relies on retinal dopamine.