Abstract
Purpose :
Dopamine plays a critical role in the retinal dark-light switch during the night-day transition. Yet, the way in which dopamine release is regulated in scotopic and mesopic lighting conditions remains unknown. Here we examine rod-mediated responses of dopaminergic amacrine cells (DACs) at a wide range of light intensities in order to understand the contribution of rods to the regulation of DAC activity.
Methods :
A transgenic mouse model in which DACs are genetically labeled with red fluorescent protein was used. The cone phototransduction pathway was genetically eliminated in this model. Possible inputs from intrinsically photosensitive retinal ganglion cells to DACs were blocked by TTX (Prigge and Zhang, 2015). In most experiments, fluorescent labeling was visualized using a multi-photon laser to minimize photopigment bleaching.
Results :
At a holding potential of -70 mV, DACs exhibited inward currents at light onset (white light, 1-s duration) with a threshold light intensity of 7.5 log quanta cm-2 s-1 (near the rod sensitivity threshold). The peak amplitude of these light-evoked currents gradually increased as the light intensity increased and reached its maximum value (55.8±25.6 pA, n=3) at 9.5 log quanta cm-2 s-1. As light intensity exceeded 9.5 log quanta cm-2 s-1, peak response amplitude remained unchanged although the responses became more prolonged. The responses lasted for ~15 s (n=3) after light off at 13.5 log quanta cm-2 s-1. In addition, rod-mediated responses of DACs were persistent during 120-s steady background illumination at both lower (8.5 log quanta cm-2 s-1, n=3) and higher (11.5 log quanta cm-2 s-1, n=3) intensities. DACs also responded to flashing lights (8.5 log quanta cm-2 s-1 at 1 Hz and 11.5 log quanta cm-2 s-1 at 0.25 Hz, n=3). Furthermore, DACs exhibited a transient outward current at light onset when the holding potential was at 0 mV. Strychnine (a glycine receptor antagonist) increased the light-evoked inward current recorded at -70 mV but attenuated the outward current measured at 0 mV, suggesting that rod-mediated responses of DACs consist of both excitatory and inhibitory components.
Conclusions :
Our results suggest that rods can mediate light-evoked activity of DACs at a wide range of light intensities, thus potentially triggering dopamine release in scotopic, mesopic or even photopic lighting conditions.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.