A key role in synchronizing daily rhythms to the day/night cycle has been traced to a light-sensitive protein in the eye, by knocking out the gene that codes for it. Mice lacking a gene for the photopigment melanopsin show a dramatic deficiency in their ability to regulate their circadian rhythms by light. The discovery, by National Institute of Mental Health (NIMH) grantees, helps unravel the heretofore elusive mechanisms by which day/night cycles regulate such rhythms in mammals. NIMH grantees Ignacio Provencio, Ph.D., Uniformed Services University of the Health Sciences (USUHS), and Steve Kay, Ph.D., The Scripps Research Institute, and colleagues report on their findings in the December 13 Science.*

In a similar knockout mouse study reported in the same issue of Science, another research team, led by NIMH grantee Norman Ruby, Ph.D., Stanford University, also found melanopsin to be a "significant contributor" to circadian function.**

Each day, a clock in the brain's hypothalamus that governs daily rhythms sleeping/waking, body temperature, eating, arousal. -- is reset by light detected in the eyes. Yet, how this works has been a mystery. Light can still reset the clock even if the rods and cones, the photoreceptors in the retina for vision, are removed, but not if the eyes are removed. Hence, scientists have hypothesized that the eyes must contain a system of photoreceptors for resetting the clock that is separate from the system for sight.

Retinal ganglion cells, which contain melanopsin, have emerged as a prime candidate only within the past year. While most of these cells are wired to parts of the brain involved in vision, about one or two percent of those in a rodent's retina project to other areas, including the clock, located in an area of the hypothalamus called the suprachiasmatic nucleus.

"Unlike the rods and cones, this light-detection system is thought to respond to the level of illumination rather than to imag
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
13-Dec-2002

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