Restoring flexibility to heal broken brains

In early life, the brain is continually sculpted by stimuli from the outside world. But soon, most neural circuits become hard-wired.

Fixed circuits are reliable but costly: the injured brain can rarely repair itself. In 2000, Stephen M. Strittmatter, M.D., Vincent Coates Professor of Neurology, identified Nogo, a protein found in the myelin sheath surrounding axons (bright green in the brain section above) that suppresses self-repair in injured neurons. A report in the September 30 issue of Science indicates that Nogo may also lock down cortical wiring during normal development.

The visual cortex is normally divided equally between inputs from each eye. But if one eye is kept shut during a “critical period” before neural circuits are fixed, the active eye appropriates more cortex. However, Strittmatter, Nigel W. Daw, Ph.D., professor of ophthalmology and visual science, and postdoctoral fellows Aaron W. McGee, Ph.D., and Yupeng Yang, Ph.D., showed that in mice bred to lack the Nogo receptor, an active eye can usurp cortical real estate well past the critical period into adulthood.

Noting that “limited plasticity is central to a range of neurological disorders,” Strittmatter is testing Nogo blockers to see if reviving the brain’s inborn flexibility can help it to heal after injury.