Effects of Non-image Forming Photoreception on Physiology and Behavior

Non-image forming (NIF) responses to light are mediated by classical photoreceptors (rods/cones) and by a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin photopigment.;Employing a specific immunotoxin, I have demonstrated that specific loss of melanopsin cells in the adult mouse retina significantly attenuates the photosensitivity of the circadian system, manifested as an inability to synchronize with the light/dark cycle. Other NIF responses, such as light induced period lengthening, are also diminished after melanopsin cell loss. Furthermore, the damage to the circadian phenotype positively correlates with the degree of loss in the number of melanopsin cells, as exemplified by a failure to entrain in a dim 12:12 LD cycle. Because loss of melanopsin from the ipRGCs does not alter NIF responses to the same extent, these findings suggest that melanopsin containing RGCs function as conduit for rod and/or cone information for certain non-image forming visual responses. Since the developed approach only requires the existence of appropriate anti-melanopsin antibodies to target ipRGCs, it eliminates the necessity of using mice as the mammalian model of melanopsin cell research due to genetic restrictions.;ipRGCs not only appear to be a conduit for rod/cone information, but they also project to multiple brain sites for which light related functions are not well understood. In this dissertation, I have suggested weight maintenance as a physiological NIF photoresponse for which melanopsin dependent photoreception appears to be instrumental. Both light itself and a compromised photoreceptive system significantly affect the ability of mice to balance their energy metabolism under a dietary challenge. More specifically, a severe weight loss profile is exhibited by melanopsin-null mice that could not be attributed to a deficiency in circadian entrainment of locomotor activity or body temperature rhythms. This phenotype appears to be rescued by the genetic ablation of rods and cones. This link between photoreception and a metabolic phenotype needs to be investigated further in order to identify the physiological/molecular mechanisms constituting it.