The effects of rod and cone loss on the photic regulation of locomotor activity and heart rate

Behavioral responses to light indirectly affect cardiovascular output, but in anesthetized rodents a direct effect of light on heart rate has also been described. Both the basis for this response and the contribution of rods, cones and melanopsin-based photosensitive retinal ganglion cells (pRGCs) remains unknown. To understand how light acutely regulates heart rate we studied responses to light in mice lacking all rod and cone photoreceptors (rd/rd cl ) along with wild-type controls. Our initial experiments delivered light to anesthetized mice at Zeitgeber time (ZT)16 (4 h after lights off, mid-activity phase) and produced an increase in heart rate in wild-type mice, but not in rd/rd cl animals. By contrast, parallel experiments in freely-moving mice demonstrated that light exposure at this time suppressed heart rate and activity in both genotypes. Because of the effects of anesthesia, all subsequent studies were conducted in freely-moving animals. The effects of light were also assessed at ZT6 (mid-rest phase). At this timepoint, wild-type mice showed an irradiance-dependent increase in heart rate and activity. By contrast, rd/rd cl mice failed to show any modulation of heart rate or activity, even at very high irradiances. Increases in heart rate preceded increases in locomotor activity and remained elevated when locomotor activity ceased, suggesting that these two responses are at least partially uncoupled. Collectively, our results show an acute and phase-dependent effect of light on cardiovascular output in mice. Surprisingly, this irradiance detection response is dependent upon rod and cone photoreceptors, with no apparent contribution from melanopsin pRGCs.