Classical MHCI Molecules Regulate Retinogeniculate Refinement and Limit Ocular Dominance Plasticity

Neuron. 2009 Nov 25;64(4):463-70. doi: 10.1016/j.neuron.2009.10.015.

Abstract

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 K(b)D(b-/-) mice, developmental refinement of retinogeniculate projections is impaired, similar to C1q(-/-) mice. These phenotypes in K(b)D(b-/-) mice are strikingly similar to those in beta2 m(-/-)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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dominance, Ocular / genetics
  • Dominance, Ocular / physiology*
  • Geniculate Bodies / growth & development*
  • Geniculate Bodies / immunology
  • H-2 Antigens / genetics
  • H-2 Antigens / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Neuroimmunomodulation / genetics
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Retina / growth & development*
  • Retina / immunology
  • Visual Pathways / growth & development
  • Visual Pathways / immunology

Substances

  • H-2 Antigens
  • H-2K(K) antigen
  • H-2Kb protein, mouse