Xiwu Zhao

Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a rare population of retinal output neurons that drives subconscious physiological responses to light, e.g. pupillary constriction, synchronization of daily rhythms to the light–dark cycle and regulation of hormone secretion. This study investigated the functional diversity among the five known types of ipRGCs, named M1–M5. We found that M2–M5 cells could detect spatial differences in light intensity, implicating an ability to analyse the form of visual stimuli. All five ipRGC types responded robustly to moving lights, and M1–M4 cells appeared to respond optimally to different speeds, suggesting they might analyse the speed of motion. M1–M4 cells were shown to project to the superior colliculus, a brain area known to detect novel objects in the visual scene, suggesting that the form and motion information signalled by these four types of ipRGCs could contribute to this visual function.

Using Flickering Light to Enhance Nonimage-Forming Visual Stimulation in Humans

PURPOSE Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate nonimage-forming visual functions such as pupillary constriction and circadian photoentrainment. Optimizing daytime nonimage-forming photostimulation has health benefits. We aimed to enhance ipRGC excitation using flickering instead of steady light. METHODS Human subjects were tested with a three-dimensional matrix of flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were measured. RESULTS Among stimuli containing 13.7 log photons cm-2, the one flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction of 48% ± 4%, 71% greater than that evoked by an equal-intensity (12.3 log photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also best for 14.7 log photons cm-2 stimuli, inducing a 58% ± 4% constriction which was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(-1)) constant light. For 15.7 log photons cm-2 stimuli, the 1-Hz, 47% duty cycle flicker was optimal although it evoked the same constriction as the best 14.7 log photons cm(-2) flicker. CONCLUSIONS Pupillary constriction depends on flicker frequency and duty cycle besides intensity. Among the stimuli tested, the one with the lowest photon count inducing a maximal response is 13.3 log photons cm(-2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design of healthier architectural lighting and better phototherapy devices for treating seasonal affective disorder and jet lag.

Mapping physiological inputs from multiple photoreceptor systems to dopaminergic amacrine cells in the mouse retina

In the vertebrate retina, dopamine is synthesized and released by a specialized type of amacrine cell, the dopaminergic amacrine cell (DAC). DAC activity is stimulated by rods, cones, and melanopsin-expressing intrinsically photosensitive retinal ganglion cells upon illumination. However, the relative contributions of these three photoreceptor systems to the DAC light-induced response are unknown. Here we found that rods excite dark-adapted DACs across a wide range of stimulation intensities, primarily through connexin-36-dependent rod pathways. Similar rod-driven responses were observed in both ventral and dorsal DACs. We further found that in the dorsal retina, M-cones and melanopsin contribute to dark-adapted DAC responses with a similar threshold intensity. In the ventral retina, however, the threshold intensity for M-cone-driven responses was two log units greater than that observed in dorsal DACs, and melanopsin-driven responses were almost undetectable. We also examined the DAC response to prolonged adapting light and found such responses to be mediated by rods under dim lighting conditions, rods/M-cones/melanopsin under intermediate lighting conditions, and cones and melanopsin under bright lighting conditions. Our results elucidate the relative contributions of the three photoreceptor systems to DACs under different lighting conditions, furthering our understanding of the role these cells play in the visual system.