Thursday, August 18, 2011

Extending Brain Plasticity and Learning into Later Life

Dendrites integrate synaptic inputs to neurons, and their branching is thought to be related to their representational capacity [24]. Branching patterns of dendritic trees are related to the degree of compartmentalization of inputs to the cell and a stronger potential for compartmentalization (i.e. more complex branching) has been proposed to increase the representational power of the cell resulting in greater learning and memory capacity [24]. Dendritic structure appears to be regulated during development in part by calcineurin [26]. Dendritic spines, which comprise the post synaptic element of over 90% of cortical excitatory synapses, are thought to be particularly important for learning and memory [18]. _ScienceDirect


An international team of researchers from Yale, University of Zagreb, and VU University in Amsterdam, have discovered that plasticity and pruning of dendritic spines in the human prefrontal cortex continues well into adulthood, throughout the 20s.
Pasko Rakic at Yale University and colleagues at the University of Zagreb, Croatia, and the VU University Medical Center in Amsterdam, the Netherlands, have now found that the brains of adults in their 20s are still subject to synaptic pruning.

Rakic's team analysed post-mortem tissue from a brain region called the prefrontal cortex (PFC) in 32 people aged between 1 week old and 91 years. Specifically, they calculated the density of dendritic spines – the tiny projections that protrude from the neuron's long dendrites, each of which facilitates communication with other neurons through a synapse.

As expected, Rakic's team found that spine density increased rapidly during infancy, reaching a peak before the 9th birthday. It then began to fall away as pruning began. Intriguingly, though, spine density did not plateau after adolescence, as might have been expected, but continued to fall gradually until the late 20s.

Rakic says the result could be good news for those hoping to gain new skills in their third decade. The period of pruning is associated with a heightened ability to learn – whether that is in picking up language skills or understanding new concepts, he says. "You should not give up learning just because you're in your 20s – it isn't too late," he says. _NewScientist
Abstract for PNAS paper

It has been shown that in rats, age related loss of normal dendritic density in prefrontal cortical neurons, occurred at the same time as loss of experience-related dendritic plasticity.

The goal of researchers is to develop ways to extend the optimal periods of brain learning well beyond young adulthood, into middle age and beyond. A Harvard - Mass General study published in Neuroscience Letters in Jan. 2011, discusses the use of a calcineurin inhibitor -- FK 506 -- to effectively increase dendritic density in cortical pyramidal neurons (all sites) of adult rats.

Such drugs provide clues as to how dendritic plasticity in the brain is regulated, and are likely to help lead to effective ways of beating back the growing impact of Alzheimer's disease and other dementias. Interestingly, calcineurin upregulation has been implicated in Alzheimer's Disease models as being responsible for amyloid related loss of glutamate receptors and decreased dendritic spine density. In such conditions, the inhibition of calcineurin (as in FK506) might well partially reverse the Alzheimer-like effects.

The mechanisms of brain development, plasticity, and disease are highly complex. We will need to learn as much as possible about signaling pathways, genetic and epigenetic mechanisms, cytoskeletal dynamics, and a number of other cellular and intercellular activities, before we will be ready to intervene in a definitive way. But things look promising, if a bit slower than we would like.


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