CHAMPAIGN, Ill. -- A five-minute flash of light in the night can reset
an animal's biological clock, say scientists who report getting closer to
understanding how that adjustment happens.
Two years ago, University of Illinois researchers reported in the journal
Science that glutamate, a common neurotransmitter produced in nerve cells,
was the messenger of light between the retina and the brain. Now, in the
Jan. 15 issue of the Journal of Neuroscience, the U. of I. team details
the earliest known molecular change that occurs in the time-shifting pathway.
Knowing how to adjust biological rhythms is of obvious interest to long-distance
air travelers, night-shift workers and people suffering from winter depression.
In the new report, based on their work administering glutamate in rats,
the researchers -- led by Martha U. Gillette, a professor of cell and structural
biology and of physiology, and Jian M. Ding, a National Institutes of Health
postdoctoral fellow -- propose a signaling pathway:
Light causes the retina to release glutamate, which binds to receptors in
a portion of the brain's hypothalamus known as the suprachiastic nucleus.
The receptor stimulates an enzyme that synthesizes nitric oxide, a gas that
can freely flow through other cell membranes. The nitric oxide, the team
discovered, activates additional enzymes that add phosphate to a nuclear
protein called CREB.
Once CREB receives the phosphate, Ding said, the pivotal message is delivered
to turn on genes that reset the clock. While additional steps may be involved,
identifying the precise genes eventually may help scientists develop artificial
techniques for readjusting daily rhythms.
As they reported two years ago, glutamate given during the day again did
not alter the animals' biological clocks, suggesting strongly that the time
of light treatment may be vitally important. The key to the sensitivity
may lie in the so-far unidentified signaling elements that occur between
the synthesis of nitric oxide and the phosphorous addition to CREB, the
scientists conclude.
"When you give an animal a flash of light at night for just five minutes,
you can permanently reset its clock," Ding said. "Such a long-lasting
behavioral change requires an alteration in gene expression. Since P-CREB
[the phosphate-containing form] is induced in five minutes after light exposure,
it is the earliest possible molecular change we've caught in a complicated
sequence of events.
"When you learn how to swim or ride a bicycle, you remember how for
the rest of your life," he added. "To the eyes of a neurobiologist,
the molecular mechanism mediating learning and memory is quite similar to
that mediating circadian rhythm phase-shifting."
The research was funded by a Public Health Service grant and by the National
Institute of Neurological Diseases and Stroke. Other U. of I. co-authors
in the January report were Lia E. Faiman, a senior research scientist, and
graduate students William J. Hurst and Liana R. Kuriashkina.