Of course, many molecules are expected change their concentration over the critical period, and many of them could be just going along for the ride without playing a role in critical period closure. If Lynx1 really was a brake, then letting up on it should enhance plasticity in older brains.
Using genetic engineering techniques, Hensch’s group went a step further -- they removed this brake in mice, and asked if their brains were still plastic past the usual critical period. Could these older brains be rewired by experience, in the manner usually seen only in young brains? To answer this, Dr. Hensch and his colleagues modified a classic experimental paradigm developed by Drs. David Hubel and Torsten Wiesel - the Nobel prize winning duo who did foundational work on the neurobiology of critical periods in the visual system.
The basic experimental approach is to record from neurons of the visual cortex of an animal - in this case a mouse - some time after one of its eyes has been sutured shut. As you might expect, depriving the visual cortex of half of its expected input is a major change in experience that can trigger changes in brain organization. Over time, more neural real estate is devoted to handling inputs from the good eye, at the expense of the bad eye. This is known as a change in “ocular dominance.”
The team found that, unlike control mice, which only undergo ocular dominance shifts if an eye is closed early in life, mice without Lynx1 still showed these shifts for eye manipulations well into adulthood. Thus, an old brain without Lynx1 is still plastic, as if the critical period had never closed. In another experiment, the group also showed that a brain without Lynx1 was also more adept at repairing itself.
While genetically eliminating Lynx1 is a sure-fire way to promote plasticity, this is unlikely to ever be the basis of ‘plasticity therapy’ in humans. Practically speaking, we can’t be re-engineered to lack Lynx1. However, another way of getting at a similar end - and one with more potential as a therapy - is to find out what the plasticity brake is acting on, and try to artificially boost the process being suppressed.
Using pharmacological and molecular labeling studies, Hensch and his colleagues found that Lynx1 works by blocking receptors for the neurotransmitter acetylcholine. Acetylcholine is infused broadly throughout the brain during intense concentration or arousal, and essentially delivers a wake up call to neurons that can prompt them to change their response properties and physical organization. By deafening neurons to these alerts, Lynx1 effectively cuts off the brain’s ability to change.
At the same time, this suggests that plasticity in later life can be enhanced by delivering drugs that boost acetylcholine levels. Indeed, Dr. Hensch’s group found that infusions of drugs that raise acetylcholine could make the mice’s brains more adaptable.
Although directly applying this to humans is probably still a ways off, it raises certain tantalizing possibilities. Naturally, most thoughts turn to some kind of ‘brain boosting’ that would help us learn certain kinds of skills with the same ease we enjoyed when we were younger. Who wouldn’t want a bit more neuro-mojo, or to be able to soak up a handful of new languages just by casually hanging out in countries we’ve always wanted to visit?
It’s not clear, though, that removing Lynx1 would necessarily spell happy times for learning complex skills and languages. These may be subject to additional, or simply different forms of regulation. Still, this research might also help with more immediate, if more modest, goals. It may be possible, for example, to use acetylcholine boosters to increase the effectiveness of brain training programs for staving off senescence and cognitive decline with age.
Are you a scientist? Have you recently read a peer-reviewed paper that you want to write about? Then contact Mind Matters editor Gareth Cook, a Pulitzer prize-winning journalist at the Boston Globe, where he edits the Sunday Ideas section. He can be reached at garethideas AT gmail.com