Learning Disability Reversed In Mice
Just as traffic signals enable safe traversing of the roadways, so too does the brain's machinery for learning and memory rely on its own stop-and-go signals. An NIMH grantee has traced a human learning disability to an imbalance in signals that increase and decrease neural activity – and demonstrated a way to correct it.
A memory is held by changes that strengthen a set of connections between nerve cells triggered by a learning event, which gets reactivated when the memory is recalled. The ability of these connections to change is critical.
In 2002, Alcino Silva, Ph.D., at the University of California Los Angeles (UCLA), and colleagues reported clues to how a single gene gone awry causes a learning disability in many people with a genetic disorder called neurofibromatosis. This spatial memory impairment is one of the most common learning disabilities caused by a single gene. The UCLA team genetically engineered mice to have a mutated version of this gene, called NF-1. As in affected humans, the mice showed a spatial memory deficit: they had problems remembering the location of an underwater platform. The researchers traced the deficit to disrupted regulation in a web of intracellular traffic signals controlling a process that strengthens the connections between nerve cells – the stuff of memory. Yet, exactly how the signal disruption interferes with this process remained unclear.
Findings of This Study
In the current study, Silva and colleagues discovered that the end result of the disrupted signals is increased release of an inhibitory chemical messenger called GABA – the brain's equivalent of a red light. Too much GABA puts the brakes on a neuron's ability to change and strengthen its connections – the critical requirement for learning and memory. When the researchers treated the mice with a GABA-blocking agent, their memory performance improved. But the researchers also discovered that learning itself boosts GABA levels.