MHCI negatively regulates synapse density during the establishment of cortical connections
Open Access
- 27 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 14 (4), 442-451
- https://doi.org/10.1038/nn.2764
Abstract
Class I major histocompatibility complex (MHCI) is known to modulate activity-dependent synaptic remodeling in the visual system and to regulate synaptic plasticity in the hippocampus. Here, the authors show that MHCI negatively regulates the density and function of cortical synapses during their initial establishment. 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 β2m−/− 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.Keywords
This publication has 48 references indexed in Scilit:
- EphB-Mediated Degradation of the RhoA GEF Ephexin5 Relieves a Developmental Brake on Excitatory Synapse FormationCell, 2010
- MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthoodProceedings of the National Academy of Sciences of the United States of America, 2010
- Classical MHCI Molecules Regulate Retinogeniculate Refinement and Limit Ocular Dominance PlasticityNeuron, 2009
- RSY-1 Is a Local Inhibitor of Presynaptic Assembly in C. elegansScience, 2009
- Semaphorin 5B mediates synapse elimination in hippocampal neuronsNeural Development, 2009
- Dynamic Aspects of CNS Synapse FormationAnnual Review of Neuroscience, 2007
- Susceptibility for homeostatic plasticity is down‐regulated in parallel with maturation of the rat hippocampal synaptic circuitryThe Journal of Physiology, 2007
- Regulation of CNS synapses by neuronal MHC class IProceedings of the National Academy of Sciences of the United States of America, 2007
- Temporal Regulation of the Expression Locus of Homeostatic PlasticityJournal of Neurophysiology, 2006
- Probing for Membrane Domains in the Endoplasmic Reticulum: Retention and Degradation of Unassembled MHC Class I MoleculesMolecular Biology of the Cell, 2002