Diagram showing a cross-section of the retina. The area near the top, labeled "Ganglionic layer", contains retinal ganglion cells, a small percentage of which contain<unk> . Light strikes the ganglia first, the rods and cones last.<unk> -containing ganglion cells, like rods and cones, exhibit both light and dark adaptation; they adjust their sensitivity according to the recent history of light exposure. However, while rods and cones are responsible for the reception of images, patterns, motion, and color,<unk> -containing ipRGCs contribute to various reflexive responses of the brain and body to the presence of light. Evidence for<unk> 's physiological light detection has been tested in mice. A mouse cell line that is not normally photosensitive, Neuro-2a, is rendered light-sensitive by the addition of human<unk> . The photoresponse is selectively sensitive to short-wavelength light (peak absorption ~479 nm), and has an intrinsic photoisomerase regeneration function that is chromatically shifted to longer wavelengths.<unk>  photoreceptors are sensitive to a range of wavelengths and reach peak light absorption at blue light wavelengths around 480 nanometers. Other wavelengths of light activate the<unk>  signaling system with decreasing efficiency as they move away from the optimum 480 nm. For example, shorter wavelengths around 445 nm (closer to violet in the visible spectrum) are half as effective for<unk>  photoreceptor stimulation as light at 480 nm.<unk>  in the iris of some, primarily nocturnal, mammals closes the iris when it is exposed to light. This local pupil light reflex (PLR) is absent from primates, even though their irises express<unk> . Mechanism When light with an appropriate frequency enters the eye, it activates the<unk>  contained in intrinsically photosensitive retinal ganglion cells (ipRGCs), triggering an action potential. These neuronal electrical signals travel through neuronal axons to specific brain targets, such as the center of pupillary control called the olivary pretectal nucleus (OPN) of the midbrain. Consequently, stimulation of<unk>  in ipRGCs mediates behavioral and physiological responses to light, such as pupil constriction and inhibition of melatonin release from the pineal gland. The ipRGCs in the mammalian retina are one terminus of the retinohypothalamic tract that projects to the suprachiasmatic nucleus (SCN) of the hypothalamus. The suprachiasmatic nucleus is sometimes described as the brain's "master clock", as it maintains the circadian rhythm, and nerve signals from ipRGCs to the SCN entrain the internal circadian rhythm to the rising and setting of the sun. The SCN also receives input from rods and cones through the retinohypothalamic tract, so information from all three photosensitive cell types (rods, cones, and ipRGCs) in the mammalian retina are transmitted to the (SCN) SCN.<unk> -containing ganglion cells are thought to influence these targets by releasing the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP) from their axon terminals.<unk> -containing ganglion cells also receive input from rods and cones that can add to the input to these pathways. Effects on circadian rhythm<unk>  serves an important role in the photoentrainment of circadian rhythms in mammals. An organism that is photoentrained has aligned its activity to an approximately 24-hour cycle, the solar cycle on Earth. In mammals,<unk>  expressing axons target the suprachiasmatic nucleus (SCN) through the retinohypothalamic tract (RHT). In mammals, the eye is the main photosensitive organ for the transmission of light signals to the brain. However, blind humans are still able to entrain to the environmental light-dark cycle, despite having no conscious perception of the light. One study exposed subjects to bright light for a prolonged duration of time and measured their melatonin concentrations. Melatonin was not only suppressed in visually unimpaired humans, but also in blind participants, suggesting that the photic pathway used by the circadian system is functionally intact despite blindness. Therefore, physicians no longer practice enucleation of blind patients, or removal of the eyes at birth, since the eyes play a critical role in the photoentrainment of the circadian pacemaker. In mutant breeds of mice that lacked only rods, only cones, or both rods and cones, all breeds of mice still entrained to changing light stimuli in the environment, but with a limited response, suggesting that rods and cones are not necessary for circadian photoentrainment and that the mammalian eye must have another photopigment required for the regulation of the circadian clock.<unk> -knockout mice display reduced photoentrainment. In comparison to wild-type mice that expressed<unk>  normally, deficits in light-induced phase shifts in locomotion activity were noted in<unk> -null mice <unk>  -/-). These<unk> -deficient mice did not completely lose their circadian rhythms, as they were still able to entrain to changing environmental stimuli, albeit more slowly than normal. This indicated that, although<unk>  is sufficient for entrainment, it must work in conjunction with other photopigments for normal photoentrainment activity. Triple-mutant mice that were rod-less, cone-less, and<unk> -less display a complete loss in the circadian rhythms, so all three photopigments in these photoreceptors, rhodopsin, photopsin and<unk> , are necessary for photoentrainment. Therefore, there is a functional redundancy between the three photopigments in the photoentrainment pathway of mammals. Deletion of only one photopigment does not eliminate the organism's ability to entrain to environmental light-dark cycles, but it does reduce the intensity of the response.
Melanopsin
Neuropeptide
Neuropil
Agouti-related peptide
Autochaperone
Bryostatin
Neurohormone
Proopiomelanocortin