MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood

Leigh A. Needleman, Xiao Bo Liu, Faten El-Sabeawy, Edward G. Jones, A Kimberley Usrey

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Immune molecules have been discovered recently to play critical roles in the development, function, and plasticity of the cerebral cortex. MHC class I (MHCI) molecules are expressed in the central nervous system and regulate activity-dependent refinement of visual projections during late postnatal development. They have also been implicated in neurodevelopmental diseases such as schizophrenia and autism. Despite the excitement generated by these unique roles for immune proteins in the brain, little is known about how these molecules regulate cortical connections. The first step toward elucidating the mechanismis to identify the spatial and temporal distribution of MHCI proteins throughout development. Using a pan-specific antibody that recognizes many MHCI variants for biochemistry and immunohistochemistry, we found that MHCI proteins are expressed in the rat visual cortex at all ages examined - during the peak of synaptogenesis, the critical period of synaptic refinement, and adulthood. Their abundance in the cortex peaked during early postnatal development, declining during periods of plasticity and adulthood. In contrast to current assumptions, pre- and postembedding immunogold electron microscopy (EM) revealed that MHCI proteins were present both pre- and postsynaptically at all ages examined. They were often found in the postsynaptic density and were closely associated with synaptic vesicles in the presynaptic terminal. These results suggest a previously undescribed model in which MHCI molecules function on both sides of the synapse to regulate connectivity in the mammalian visual cortex before, during, and after the establishment of connections.

Original languageEnglish (US)
Pages (from-to)16999-17004
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
StatePublished - Sep 28 2010


  • HLA
  • MHCI
  • Neuroimmunology
  • Synapse elimination
  • Synapse formation

ASJC Scopus subject areas

  • General
  • Medicine(all)


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