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 language | English (US) |
|---|---|
| Pages (from-to) | 442-451 |
| Number of pages | 10 |
| Journal | Nature Neuroscience |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2011 |
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ASJC Scopus subject areas
- Neuroscience(all)
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MHCI negatively regulates synapse density during the establishment of cortical connections. / Glynn, Marian W.; Elmer, Bradford M.; Garay, Paula A.; Liu, Xiao Bo; Needleman, Leigh A.; El-Sabeawy, Faten; Usrey, A Kimberley.
In: Nature Neuroscience, Vol. 14, No. 4, 04.2011, p. 442-451.Research output: Contribution to journal › Article
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TY - JOUR
T1 - MHCI negatively regulates synapse density during the establishment of cortical connections
AU - Glynn, Marian W.
AU - Elmer, Bradford M.
AU - Garay, Paula A.
AU - Liu, Xiao Bo
AU - Needleman, Leigh A.
AU - El-Sabeawy, Faten
AU - Usrey, A Kimberley
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
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U2 - 10.1038/nn.2764
DO - 10.1038/nn.2764
M3 - Article
C2 - 21358642
AN - SCOPUS:79953191735
VL - 14
SP - 442
EP - 451
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 4
ER -