2009 : WHAT WILL CHANGE EVERYTHING?

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Vice President of Research, George Washington University
CONTROLLING BRAIN PLASTICITY

In the 1960s movie "The Graduate" a young Dustin Hoffman is advised to go into plastics, presumably because that will be the next big thing.

Today, one might well advise the young person planning to pursue a degree in medicine or the biological sciences to go into brain plasticity. This refers to the fact that neurons are malleable throughout life, capable of being shaped by external experiences and endogenous events.

Recent imaging studies of single neurons have revealed that specialized parts of nerve cells, termed dendritic spines are constantly undergoing a process of rapid expansion and retraction. While brain cells are certainly capable of structural and functional changes throughout life, an extensive scientific literature has shown that plasticity in the nervous system is greatest early in development, during the so-called critical periods. This accounts for the marvelous ability of children to rapidly master various skills at different developmental stages. Toddlers have no difficulty in learning two, three and even more languages, and most adolescents can learn to ski black diamond slopes much before their middle-aged parents. The critical periods underlying such learning reflect the high degree of plasticity exhibited by specific brain circuits during the first two decades of life.

In recent years, developmental neurobiologists have made considerable progress in unraveling the myriad factors underlying the plasticity of neurons in the developing brain. For instance, a number of studies have now demonstrated that it is the formation of inhibitory circuits in the cortex that causes decreased plasticity in the maturing visual system. While no single event can entirely explain brain plasticity, progress is being attained at a rapid pace, and I am convinced that in my lifetime we will be able to control the level of plasticity exhibited by mature neurons.

Several laboratories have already discovered ways to manipulate the brain in ways to make mature neurons as plastic as during early development. Such studies have been done using genetically engineered mice with either a deletion or an over-expression of specific genes known to control plasticity during normal development. Moreover, drug treatments have now been found to mimic the changes observed in these mutant mice.

In essence this means that the high degree of brain plasticity normally evident only during early development can now be made to occur throughout the life span. This is undoubtedly a game changer in the brain sciences. Imagine being able to restore the plasticity of neurons in the language centers of your brain, enabling you to learn any and all languages effortlessly and at a rapid pace. The restoration of neuronal plasticity would also have important clinical implications since unlike in the mature brain, connections in the developing brain are capable of sprouting (i.e. new growth). For this reason, this technology could provide a powerful means to combat loss of neuronal connections, including those resulting from brain injury as well as various disease states.

I am optimistic that these treatments will be forthcoming in my lifetime. Indeed a research group in Finland is about to begin the first clinical study to assess the ability of drug treatments to restore plasticity to the visual system of adult humans. If successful this would provide a means for treating amblyopia in adults, a prevalent disorder of the visual system, which today can only be treated in young children whose visual cortex is still plastic. 
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Still there are a number of factors will need to be worked out before the restoration of neuronal plasticity becomes a viable procedure. For one thing, it will be necessary to devise a means of targeting specific groups of neurons, those controlling a function that one wants to attain enhanced plasticity. Many people might wish to have a brain made capable of effortlessly learning foreign languages, but few would be pleased if this were accompanied by a vocabulary limited to babbling sounds, not unlike those of my granddaughter who is beginning to learn to speak English and Ukrainian.