Spontaneous activity before birth drives brain wiring

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Photo by Creative Commons.

Using light stimuli on newborn mice, Yale researchers have illuminated how the nervous system linking the eyes and brain develops.

Research by a Yale team led by Michael Crair, William Ziegler III Associate Professor of Neurobiology, suggests that before a baby is born, brain development is affected by activity in immature neural circuits. The study, published Dec. 18 in the journal Nature Neuroscience, revealed that the closed eyes of a unborn baby produce messages that hold the key to proper wiring of the visual system prior to birth. Crair said the development of other brain pathways in embryos might follow a similar pattern, and the research could help scientists better understand the causes of neurodevelopmental conditions such as autism.

“There was speculation based on theories about how activity might shape brain development,” Crair said. “[But] nobody has previously manipulated the temporal pattern of activity in the two eyes in vivo, and examined the consequences on brain wiring.”

Using newborn mice with certain cells in the retina engineered to respond to light, the team flashed bursts of light to activate each eye. The experiments simulated spontaneous waves of activity that are known to be generated within the eyes before the baby leaves the womb.

The researchers found that when both the eyes were simultaneously activated, the wiring of the eyes to parts of the brain responsible for vision went awry, while activating each eye in succession improved the wiring of the eyes to the brain.

“Our work suggests that, even when a human baby is still in the womb, neuronal activity, whether spontaneous or sensory-driven, can shape brain circuit development,” Crair said. He said the brain development that occurs in newborn mice is analogous to that of late-term human embryos, so they were likely to have similar mechanisms of neurological development.

Crair said similar rhythmic spontaneous activity exists in many other developing neural circuits, including the spinal cord and parts of the brain, and that this experiment suggests that timing patterns may also be important for proper wiring in these other areas.

Marla Feller, neurobiology professor at UC Berkeley, called the discovery an “incredibly exciting” result, because it demonstrated that pre-birth neurological activity effected brain development.

“It used to be thought that when a baby is born and when it’s exposed to the environment, that’s when neural activity becomes important for the brain’s development,” Feller said. “Although people have known for a while that there was periodic and spontaneous activity [before birth], nobody knew how important it was.”

Crair said this discovery could have implications in neurodevelopmental diseases such as autism, which Crair thinks is a result of brain miswiring, and could be caused by abnormal patterns of spontaneous activity in the developing brain. He added that that possibility is “completely unexplored right now.”

Calling the experiment technically impressive and well-controlled, Feller said it will have a huge impact on the field. She agreed with Crair’s suggestion of its implications for diseases such as autism.

Daniel Kerschensteiner, ophthalmology and visual sciences professor at Washington University in St. Louis, said the study’s findings have potential to counteract faulty wiring in brain disorders or help re-establish neural connections after injury to the nervous system.

Crair said his lab is now trying to learn more about the precise nature of the spontaneous activity.

The research was funded by grants from the U.S. National Institutes of Health, Research to Prevent Blindness and the family of William Ziegler III, late chairman of Swisher, a cigar company.

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