Making an Old Brain Young

Dec. 2, 2008— -- New ways to manipulate neural plasticity--the brain's ability to rewire itself--could make adult brains as facile as young ones, at least in part. Drugs that target these mechanisms might eventually help treat neurological disorders as diverse as Alzheimer's, stroke, schizophrenia, and autism. But first scientists will need to figure out how to harness this rewiring capacity without damaging vital neural circuitry.

"Once we understand the mechanisms behind plasticity, we can design therapies to tap into it more specifically," says Joshua Sanes, a neuroscientist at Harvard Medical School.

The brain experiences a "critical period" of heightened malleability during development, when outside experiences--such as sights and sounds--are necessary for different brain systems to develop normally. Infants and toddlers between the ages of one and three need regular visual stimuli, for example, in order for their visual systems to form the appropriate neural circuits. If one eye is impaired during this time, such as with lazy eye (also called amblyopia), vision may be permanently faulty.

Studying the equivalent of lazy eye in rodents, Takao Hensch and his colleagues at Children's Hospital Boston discovered two mechanisms that control this critical period. While some drugs were already known to accelerate the onset of this critical period--for example, valium, an anxiety drug that targets the brain's inhibitory signaling system--Hensch's work helps explain why and provides specific targets for new treatments.

Like children, rodents with one eye covered during their critical period never recover normal sight. Scientists use this fact to measure treatments that affect the timing of developmental neural plasticity. Treatments that extend the critical period, for example, allow adult animals reared with only one functioning eye to regain normal sight. Hensch's group has previously shown that a specific cell type, called a large basket cell, triggers the onset of neural plasticity. These cells are surrounded by molecular nets. "The critical period ends when the net wraps around [the cells] very tightly," says Hensch. So molecularly severing the nets with an enzyme called chondroitinase can restore plasticity in adults.