Nerve cells in the brain can rewire and fine-tune themselves by forming connections with neighboring cells. Xenopus tadpoles. Images courtesy of Science. Researchers from Montreal Neurological Institute at McGill University and the McGill University Health Center have demonstrated exactly how this happens using timed visual stimulation and multi-photon laser-scanning microscopy. This is the first time that such evidence has been observed in real time, researchers said. They said the findings support the Hebbian model of nerve circuit formation, which holds that cells that fire in unison form strong, stable connections, while cells that are out of synch will destabilize and withdraw from any connections. The McGill team examined brain development in Xenopus tadpoles, which are transparent. Optical fibers with different light patterns were used to stimulate the tadpoles’ eyes as the researchers imaged and recorded nerve cell branch formation. The researchers found that asynchronous firing caused brain nerve cells to lose their ability to make other cells fire, and also caused an increased elaboration of new branches in search of better-matched partners. Asynchronous activation of the tadpoles’ eyes shows nerve cell branch formation. “The surprising and entirely unexpected finding is that even though nerve circuit remodeling from asynchronous stimulation actively weakens connections, there is a 60 percent increase in axon branches that are exploring the environment, but these exploratory branches are not long-lived,” said Dr. Edward Ruthazer, an associate professor of neurology and neurosurgery at MNI. Synchronous stimulation, on the other hand, appears to stabilize retinal nerve cell branches and activate the neurotransmitter receptor N-methyl-D-aspartate. The receptor does not appear to be involved in the nerve branch formation associated with asynchronous stimulation. The researchers have been studying the formation of brain circuitry during development to better understand healthy brain wiring. They also hope such studies will lead to development of more effective treatments for nervous system injuries, as well as therapies for neurodevelopmental disorders such as autism and schizophrenia. The research is published in Science (doi: 10.1126/science.1251593). For more information, visit www.mni.mcgill.ca.