Source:
STANFORD, Calif. - Molecules assumed to be in the exclusive employ of the immune system have been caught moonlighting in the brain - with a job description apparently quite distinct from their role in immunity.

Carla Shatz, PhD, professor of neurobiology and of biology, and her colleagues at the Stanford University School of Medicine have shown that members of a large family of proteins critical to immune function (collectively known as HLA molecules in humans and MHC molecules in mice) also play a role in the brain. "We think that this family of molecules has an important role in learning and memory," Shatz said. Surprisingly, the absence of one or another of them in the brain can trigger improved motor learning, although perhaps at the expense of other learning ability.

The study will be published online on March 30 in the journal Proceedings of the National Academy of Sciences. . . .

n the new study, the Shatz laboratory looked at mice's ability to learn how to keep from falling off a rotating rod called a rotarod. "It's like a circus trick," said Shatz. First author Mike McConnell, a postdoctoral researcher now at the Salk Institute in La Jolla, Calif., put two batches of mice - normal ones, and bioengineered mice that lacked the "K" and "D" proteins - through their paces on the rotarod without knowing which batch was which. He noticed that one batch was consistently superior at learning the task. A week later he retested them, with the same results. After another three-month rest, the early winners continued to excel while the slower group had to relearn the rotarod routine pretty much from scratch.

When the identity of the two mouse groups was revealed, it turned out that the good learners were the mutant mice. Looking closely at the mice's cerebellar circuitry, the researchers also discovered that contacts between Purkinje cells and the cells feeding them inputs were altered more easily in the K- and D-deficient mice than in the normal ones.

"This proves that changes in levels of these two MHC molecules is enough to account for both changes in motor learning and the ease of strengthening or weakening connections in the cerebellum," Shatz said. "It implies that, normally, these molecules are putting a brake on the nervous system's ability to alter its circuitry in response to changing experiences. When you take the MHC molecules away, you remove the brake."

In the wild state, motor performance - running from predators, chasing down meat - is a nice thing to have. If the K- and D-deficient mice learn and retain motor skills better, why doesn't evolution select for the deficient mice? Said Schatz: "Several other forms of learning besides motor learning - cognitive learning, spatial learning, recognition - don't take place in the cerebellum. There may be tradeoffs between one kind of learning and another - you're better able to escape but don't know exactly what to do in the next environment you encounter after running away - as well as between learning ability and circuit stability. More-easily altered circuitry might also be more prone to epilepsy."

The Stanford researchers have found other MHC molecules expressed in other types of neurons in other parts of the brain. "These molecules keep showing themselves to be important in limiting how much circuits can change by strengthening or weakening connections between nerve cells. (Source)