The brain is a hotbed of electrical activity. Scientists have long known that brain cells communicate via electrical missives, created by charged atoms and molecules called ions as they travel across the membranes of those cells. But a new study suggests that in the days and weeks that lead up to a brain forming in an embryo or fetus, altering the electrical properties of these cells can dramatically change how the ensuing brain develops.



Researchers at Tufts University and the University of Minnesota have investigated how the difference in charge on either side of a resting cell’s membrane—its electrical potential—helps build the brain. In previous work Tufts University developmental biologist Michael Levin found that patterns of electrical potentials in the earliest stages of an embryo’s development can direct how an animal’s body grows, and that manipulating those potentials can cause a creature to sprout extra limbs, tails or functioning eyes. Now, Levin’s group has investigated how these potentials shape the brain.



Working with frog embryos the researchers first used dyes to see the patterns of electrical potentials that precede brain development. They noticed that before the development of a normal brain the cells lining the neural tube, a structure that eventually becomes the brain and spinal cord, have extreme differences in ionic charge within and outside the membrane that houses the cells. In other words, these cells are extremely polarized.



Next Levin and his colleagues injected genetic material into some cells to spur the development of additional ion channels in the membrane. The channels allow charged atoms and molecules to travel into or out of cells; the extra channels enabled ions to cross more easily, thereby reducing how polarized these cells had become. In turn these electrical changes caused the brain to develop abnormally, with certain brain regions growing in too small or completely failing to develop. The observations led the team to conclude that the pattern of potentials they had disrupted may be a key component to healthy brain development, a bioelectrical blueprint for the brain.



Deeper study, as detailed in their paper in The Journal of Neuroscience on March 10, revealed that even the patterns of electrical potential in cells far from the neural tube were crucial to normal growth. The researchers also identified the molecular mechanisms—particularly the role of signals from calcium ions—involved in this effect.



University of California, San Diego neurobiologist Nicholas Spitzer, who did not participate in this study but has studied the brain’s electrical signaling extensively, finds the research convincing and notes that this mechanism-level understanding helps clarify ongoing questions about electricity’s part in shaping the brain. He suspects that future work will uncover an even greater role for such signaling.



As in their previous studies of limbs and eyes, Levin and his colleagues tested the strength of their bioelectrical blueprint elsewhere in the body to see whether it would spur neuronal growth in locations far from the brain. Although they could not grow a second brain elsewhere in the body, they succeeded in growing full neural tissue. “I think this is really amazing—equally important as the growth of additional eyes,” says University of California, Davis, biologist Min Zhao (also unaffiliated with the study) who investigates the application of electrical fields in wound healing.



In addition, Levin and his colleagues worked with a frog population carrying a genetic defect that would cause abnormal brain growth. They confirmed that these frogs exhibited abnormal electrical patterning during early development. By treating the animals with drugs that target specific ion channels, the researchers could restore normal patterns to ensure healthy brain growth, rescuing the brain from its genetic fate.



Altogether the findings could inspire novel interventions to heal the brain, whether to regenerate brain cells lost to degenerative disease or in remedying birth defects due to environmental toxins. In contrast to targeting genetic sources of dysfunction, Levin believes electrical manipulation could serve as a larger-level and more efficient control dial for brain development.



The work also furthers our understanding of the interplay between genes, chemistry and electricity in the brain’s earliest stages. “These are issues in brain development that people never talk about,” Levin says. “This work could provide a road map for new approaches.”