TY - JOUR
T1 - Classical MHCI Molecules Regulate Retinogeniculate Refinement and Limit Ocular Dominance Plasticity
AU - Datwani, Akash
AU - McConnell, Michael J.
AU - Kanold, Patrick O.
AU - Micheva, Kristina D.
AU - Busse, Brad
AU - Shamloo, Mehrdad
AU - Smith, Stephen J.
AU - Shatz, Carla J.
N1 - Funding Information:
We thank members of the Shatz lab for helpful suggestions, comments, and technical assistance. β2m −/− TAP1 −/− mice were a gift from D. Raulet (UC Berkeley) and K b D b−/− mice from H. Ploegh (MIT). We thank Dr. Beth Stevens (Harvard Medical School) for the C1q antibody and helpful discussions on Array Tomography. Thanks also to Matthew Priestley and Nay Lui Saw of the Stanford Institute for Neuroinnovation and Translational Neuroscience NeuroBehavior Core Facility. This work was supported by NIH R01 EY02858, NIH R01 MH071666, the G. Harold and Leila Y. Mathers Charitable Foundation, the Dana Foundation (C.J.S. and A.D.), and NIH T32CA09361 (M.J.M.).
PY - 2009/11/25
Y1 - 2009/11/25
N2 - 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-Kb and H2-Db, ocular dominance (OD) plasticity is enhanced. Mice lacking PirB, an MHCI receptor, have a similar phenotype. H2-Kb and H2-Db 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 KbDb-/- mice, developmental refinement of retinogeniculate projections is impaired, similar to C1q-/- mice. These phenotypes in KbDb-/- mice are strikingly similar to those in β2 m-/-TAP1-/- mice, which lack cell surface expression of all MHCIs, implying that H2-Kb and H2-Db can account for observed changes in synapse plasticity. H2-Kb and H2-Db ligands, signaling via neuronal MHCI receptors, may enable activity-dependent remodeling of brain circuits during developmental critical periods.
AB - 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-Kb and H2-Db, ocular dominance (OD) plasticity is enhanced. Mice lacking PirB, an MHCI receptor, have a similar phenotype. H2-Kb and H2-Db 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 KbDb-/- mice, developmental refinement of retinogeniculate projections is impaired, similar to C1q-/- mice. These phenotypes in KbDb-/- mice are strikingly similar to those in β2 m-/-TAP1-/- mice, which lack cell surface expression of all MHCIs, implying that H2-Kb and H2-Db can account for observed changes in synapse plasticity. H2-Kb and H2-Db ligands, signaling via neuronal MHCI receptors, may enable activity-dependent remodeling of brain circuits during developmental critical periods.
KW - MOLIMMUNO
KW - MOLNEURO
KW - SIGNALING
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U2 - 10.1016/j.neuron.2009.10.015
DO - 10.1016/j.neuron.2009.10.015
M3 - Article
C2 - 19945389
AN - SCOPUS:70449758396
SN - 0896-6273
VL - 64
SP - 463
EP - 470
JO - Neuron
JF - Neuron
IS - 4
ER -