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‘Clock’ genes set time for brain development

by John Lorinc
Apr 6 / 15

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The genes that help determine when we go to sleep and when we wake up also help regulate the development of our brains, opening and closing critical developmental windows throughout childhood.

Takao Hensch
Takao Hensch has discovered how genes that regulate circadian rhythms also play a role in opening critical learning windows in the brain.

So-called “clock” genes manufacture molecules that are vital to setting circadian rhythms, including our sleep cycles. But the genes are also active in other cells in the brain and body. Now Takao K. Hensch (Harvard University), a senior fellow in CIFAR’s program in Child & Brain Development, working with post-doctoral fellow Yohei Kobayashi and colleagues, has shown that the genes are important in the function of parvalbumin cells, which help regulate brain plasticity.

“This cell is the trigger cell for critical periods. It’s like throwing a switch,” Hensch says.

When mice lacked these clock genes, the researchers were able to show that their visual development was delayed. This suggested that intrinsic factors affected brain plasticity along with external factors, such as lack of exposure to light at an early age. Hensch says that the pace of development is determined by an interaction between the internal clock and external environmental influences.

These findings, along with ongoing but as yet unpublished research, suggest that circadian clock genes affect a broader range of developmental and sensory changes, including hearing, smell, and touch, and the brain’s ability to process multiple sensory inputs simultaneously. Brain development may be guided by a series of internal genetic clocks, operating at different speeds and cycles throughout life, Hensch says.

The discovery has significant implications for understanding the processes that lead to developmental disorders or certain mental illnesses, including autism and schizophrenia.

Previous research had found that patients with these problems often suffered from sleep disorders, reflecting some kind of malfunctioning in the circadian system. The latest findings offer a new perspective on this finding, suggesting mistimed development as a consequence of clock gene impairment.

The work also points to possibilities at the other end of life. “We’ve been looking at what might turn off the clock” in older people with degenerative brain conditions and how those cells might be rejuvenated. “We haven’t done that yet,” Hensch says. “Switching on the clock gene system becomes an interesting target.”