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New retinal receptor

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The results, published in Neuron, are a surprise. Though rods and cones, their biological cousins in the retina, clearly adjust to light levels, these new cells – intrinsically photosensitive retinal ganglion cells, or ipRGCs – were assumed not to adapt this way. Still, the adaptation process in ipRGCs is weaker and slower than it is in rods and cones.

The findings provide further evidence that the eye has complementary brain-signaling systems at work. Rods and cones rapidly communicate changes in brightness, signals which allow us to glimpse a baseball streaking across the sky or a deer darting into a darkened road. But ipRGCs work differently. They send signals about overall brightness, telling the brain when it is night and when it is day.

"These cells operate like a light meter on a camera," said David Berson, the Sidney A. Fox and Dorothea Doctors Fox Professor of Ophthalmology and Visual Sciences. "They tell the brain to constrict the pupil based on the amount of light registered over time."

Berson discovered ipRGCs in his Brown neuroscience lab three years ago. These cells number no more than 2,000 in the eye and have a direct link to the brain, sending electrical messages to an area regulating the pupil as well as a region controlling the body clock. This circadian rhythm controls alertness, sleep, hormone production, body temperature and organ function.

Earlier this year, the Berson lab reported in Nature that a protein called melanopsin plays a key role in the cells' ability to absorb light energy, sparking a chain reaction that sends these signals to the brain.

But how ipRGCs behave naturally is largely unknown. The authors said this new work fills in a few blanks in the scientific book.

Intrinsically photosensitive retinal ganglion cells – ipRGCs – shown in this lab image of cell bodies and their dendrites from the eye of a mouse, constrict the pupil and give the brain information about circadian rhythms. (Photo: David Berson/Brown University)
"Until now, we didn't know if these cells were adaptive to lighting conditions," said Kwoon Wong, a postdoctoral research fellow in the Berson lab and the lead author of the Neuron paper. "Now we know that they are. Compared with rods and cones, they're glacially slow and they don't adjust their sensitivity as completely. But they do behave in similar ways. It's a difference of degree, not of kind. In fact, what we found out about ipRGCs seems to be true of all biological systems: They adapt to their environment."

To arrive at the findings, Wong, Berson and former Brown undergraduate Felice Dunn exposed rat ipRGCs to a series of increasingly bright flashes then measured changes in voltage across the cell membrane – a sign of neuronal response. The flashes evoked much bigger responses when the cells had been sitting in darkness than when they were exposed to bright background light. These adjustments persisted when ipRGC synapses were chemically blocked, indicating that the changes in sensitivity were indeed happening within these cells.

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