You wouldn't want a car with no brakes. It turns out that the developing brain needs them, too.
Researchers at the Stanford University School of Medicine have identified a set of molecular brakes that stabilize the developing brain's circuitry. Moreover, experimentally removing those brakes in mice enhanced the animals' performance in a test of visual learning, suggesting a long-term path to therapeutic application.
In a study to be published Nov. 25 in Neuron, Carla Shatz, PhD, professor of neurobiology and of biology, and her colleagues have implicated two members of a large family of proteins critical to immune function (collectively known as HLA molecules in humans and MHC1 molecules in mice) in brain development. Until recently, these immune-associated molecules were thought to play no role at all in the healthy brain.
In previous studies, Shatz and her co-investigators have shown that MHC molecules are found on the surfaces of nerve cells in the brain, and that they temper "synaptic plasticity": the ease with which synapses - the more than 100 trillion points of contact between nerve cells that determine brain circuitry - are strengthened, weakened, created or destroyed in response to experience. In one recent study, the Shatz group tied two specific members of the MHC1 family, called K and D, to the ability of circuits in a brain region responsible for motor learning to be refined by a learning experience.
This time, the scientists looked at vision processing in the brain. "We'd already found that K and D were located in brain regions we knew mattered: the visual cortex, and a relay station in the brain that sends its input to the visual cortex," said Shatz.
A good example of the "use it or lose it" manner in which experience-dependent circuit tuning shapes the brain is the ability of one eye to take over brain circuits that normally would be used by the other eye.
"Normally, your two eyes share vision-devoted brain circuits 50/50," Shatz said. "But when kids are born with a congenital cataract, or lose an eye - or in animal models where one eye is blocked - so that the brain's visual-information-processing machinery is no longer being used evenly by both eyes, the other eye doesn't just sit there. It takes over the machinery normally reserved for input from the other eye."
In order to map the roles of K and D in visual development, Shatz's group studied mice genetically engineered to lack these two molecules. They found that developmental circuit tuning was abnormal, she said. "The nerve input from the eyes was the same at the gross level - the major nerve tracts still went from the eye to the first visual relay system, and from there to the visual cortex. But the detailed connections within each structure had been altered. The adult patterning didn't develop normally."
In these K- and D-deficient mice, the capacity of a more-used eye to dominate visual information-processing circuitry is abnormal, and in a surprising way, said Shatz. "There's too much of it," she said. "If one eye stops functioning, the other eye takes over more than its fair share of the cortical machinery devoted to the brain's visual-information-processing territory."