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 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.
Datwani
Akash
A
Departments of Biology, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
McConnell
Michael J
MJ
Kanold
Patrick O
PO
Micheva
Kristina D
KD
Busse
Brad
B
Shamloo
Mehrdad
M
Smith
Stephen J
SJ
Shatz
Carla J
CJ
D000818:Animals; D000831:Animals, Newborn; D023882:Dominance, Ocular / Q000235:genetics / Q000502:physiology*; D005829:Geniculate Bodies / Q000254:growth & development* / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D015213:Neuroimmunomodulation / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000254:growth & development* / Q000276:immunology; D014795:Visual Pathways / Q000254:growth & development / Q000276:immunology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse