Classical MHCI Molecules Regulate Retinogeniculate Refinement and Limit Ocular Dominance Plasticity

Major histocompatibility complex class I (MHCI) genes were discovered unexpectedly in healthy CNS neurons in a screen for genes regulated by neural activity. In mice lacking just 2 of the 50+ MHCI genes H2-K-b and H2-D-b, ocular dominance (OD) plasticity is enhanced. Mice lacking PirB, an MHCI receptor, have a similar phenotype. H2-K-b and H2-D-b are expressed not only in visual cortex, but also in lateral geniculate nucleus (LGN), where protein localization correlates strongly with synaptic markers and complement protein C1q. In (KDb-/-)-D-b mice, developmental refinement of retinogeniculate projections is impaired, similar to C1q(-/-) mice. These phenotypes in (KDb-/-)-D-b mice are strikingly similar to those in beta 2m(-/-)TAP1(-/-) mice, which lack cell surface expression of all MHCIs, implying that H2-K-b and H2-D-b can account for observed changes in synapse plasticity. H2-K-b and H2-D-b ligands, signaling via neuronal MHCI receptors, may enable activity-dependent remodeling of brain circuits during developmental critical periods.