A human brain. The presence of a protein called PirB helps make the connections between its cells stable.

Credit: National Institute of Mental Health

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SYDNEY, 31 August 2006: A protein normally associated with the immune system could hold a clue to one of the great puzzles of neuroscience: why you can't teach old dogs new tricks. The study, published in the U.S. journal Science, could even create hope for people suffering spinal cord injuries and brain damage.

Plasticity in the brain is its ability to rewire internal connections as a result of experience. Normally this plasticity is largely restricted to critical periods of development early in life, meaning puppies are more receptive to learning tricks.

Now researchers at the Harvard Medical School in Boston have shown that adult mice who lack the protein ‘paired-immunoglobulin like receptor-B' (PirB), have brains that retain the plasticity of much younger mice, suggesting that PirB somehow inhibits this plasticity. Put another way, mice that have the PirB protein are less able to make new connections.

The brains of younger mice lacking PirB also exhibit greater plasticity than those endowed with the protein. Taken together, these results have important implications for the future study of brain injury and repair, according to the researchers.

"Our study of mutant mice lacking PirB function reveals that at all ages - even critical periods where circuits are prone to change - there are active molecular mechanisms that function to limit synaptic plasticity," said Josh Syken, lead author of the study.

"The implications here should attract broad interest outside the field of developmental neuroscience, because molecules and mechanisms that oppose neuronal plasticity represent new targets for therapy to re-establish damaged connections following spinal cord injury, head injury or stroke."

Syken said he investigated immune system proteins because previous research had suggested they may be involved. In the immune system, ‘major histocompatibility complex Class I' proteins teach immune cells which cells to attack by interacting with receptors on their surface. In brain cells, production of these MHC Class I proteins are stimulated by activity in the cell, and in fact are required for normal synaptic plasticity.

Using a technique called 'in situ hybridisation', the researchers found that the MHC Class I receptor PirB is expressed widely throughout the brain at all ages. To determine how the protein functions, they generated a mouse deficient in PirB, and focused their study on the part of the brain that controls vision.

Syken and his colleagues sewed one eye shut in their adult PirB-deficient mice, and also in controls, for several days. They then exposed the open eye to light and examined which neurons in the brain were activated. The PirB-deficient adults showed an expansion of the area of the visual cortex which responded to the open eye, suggesting that new connections had formed. They repeated the experiment with immature mice and found, unexpectedly, that plasticity was enhanced even in the younger brain.

"Other factors have been shown to restrict plasticity after the critical period, but we believe that this is one of the first proteins to act in this way throughout life," said Syken.