MHCI negatively regulates synapse density during the establishment of cortical connections

Marian W. Glynn, Bradford M. Elmer, Paula A. Garay, Xiao Bo Liu, Leigh A. Needleman, Faten El-Sabeawy, A Kimberley Usrey

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Abstract

Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in 22m mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of excitation and inhibition onto cortical neurons. sMHCI levels were modulated by activity and were necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity altered synapse density exclusively during early postnatal development. These results identify a previously unknown function for immune proteins in the negative regulation of the initial establishment and function of cortical connections.

Original languageEnglish (US)
Pages (from-to)442-451
Number of pages10
JournalNature Neuroscience
Volume14
Issue number4
DOIs
StatePublished - Apr 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

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Glynn, M. W., Elmer, B. M., Garay, P. A., Liu, X. B., Needleman, L. A., El-Sabeawy, F., & Usrey, A. K. (2011). MHCI negatively regulates synapse density during the establishment of cortical connections. Nature Neuroscience, 14(4), 442-451. https://doi.org/10.1038/nn.2764