Science Daily: A gene called Npas4, already known to play a key role in balancing excitatory and inhibitory inputs in brain cells, appears to also be a master timekeeper for the brain’s circadian clock, new research led by UT Southwestern scientists suggests.

The finding, published online today in Neuron, broadens understanding of the circadian clock’s molecular mechanisms, which could eventually lead to new treatments for managing challenges such as jet lag, shift work, and sleep disorders.

“To reset the circadian clock, you ultimately need to reset its molecular gears,” said study leader Joseph S. Takahashi, Ph.D., Professor and Chair of Neuroscience at UTSW and a Howard Hughes Medical Institute Investigator. “This study suggests that Npas4 might be one of the most important components for resetting the clock to light.”

For decades, researchers have known that a brain region called the suprachiasmatic nucleus (SCN) is responsible for controlling circadian rhythms, the various cycles of activity that typically run on a 24-hour basis. These rhythms are entrained by light, Dr. Takahashi explained; cells in the SCN respond to signals relayed by the retina, the eye’s light-sensitive tissue. However, the molecular basis of this phenomenon is not well understood.

To better understand how the SCN sets circadian rhythms, the researchers used a technique called single-nucleus sequencing to look at gene activity in individual cells in mice after the animals were exposed to light. Dr. Takahashi and his colleagues found that three different subpopulations of SCN neurons respond to light stimulation. A common thread tying these subtypes together was increased activity in genes that respond to neuronal PAS domain protein 4 (NPAS4), the protein made by the Npas4 gene.

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