Brain rewiring

The brain forms complex new circuits after damage, often far from the injured site, to compensate for loss of function.

This finding by researchers from the University of California Los Angeles, Drs Moriel Zelikowsky and Michael Fanselow, and Dr Bryce Vissel, from the Garvan Institute of Medical Research in Sydney, is the first demonstration of such circuit plasticity.

It is widely accepted that the multiple circuits in the brain are independent and dedicated to performing a specific function involving specific information. For example, it is thought that different circuits specialise in integrating and storing different classes of memories.

However, the brain can also behave dynamically, as seen in studies looking at learning following brain damage.

In this work, exact regions of the brain were identified that take over when the learning and memory centre of the brain, the hippocampus, is damaged.

It was found that rats were able to learn new tasks after damage to the hippocampus. And although they needed more training, the rats nonetheless learned from their experiences, a surprising finding.

Analysis of the anatomy of the changes that had taken place in the rat brains revealed significant functional changes in two regions of the pre-frontal cortex.

“Interestingly, previous studies had shown that these prefrontal cortex regions had been reported to light up in the brains of people with Alzheimer’s, suggesting that similar compensatory circuits develop in people,” said Vissel.

Vissel, whose work centres on examining the potential for hippocampal regeneration and repair in Alzheimer’s patients, believes the finding will radically change the ways in which scientists think about the brain.

“Until now, we’ve been trying to figure out how to stimulate repair within the hippocampus. Now we can see other structures stepping in, and whole new brain circuits coming into being. That’s truly exciting,” he said.

The work revealed that subregions of the prefrontal cortex compensated in different ways - the infralimbic cortex silenced its activity whereas the prelimbic cortex increased its activity.

Understanding how to differentially enhance and silence function, behaviourally or pharmacologically, will be needed to harness this kind of plasticity to help stroke victims or people with Alzheimer’s.

“It’s clearly important not to enhance all areas. The brain works by silencing and activating different populations of neurons. To form memories, you have to filter out what’s important and what is not - in other words, you need to keep the background noise down in order to detect similar patterns," said Zelikowsky.

This work was published in the early online edition of the Proceedings of the National Academy of Sciences (PNAS).