MHCI negatively regulates synapse density during the establishment of cortical connections.
MHCI negatively regulates synapse density during the establishment of cortical connections.
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DOI：
10.1038/nn.2764
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发表时间：
2011-04
影响因子：
25
通讯作者：
McAllister, A. Kimberley
中科院分区：
文献类型：
--
作者：
Glynn, Marian W.;Elmer, Bradford M.;Garay, Paula A.;Liu, Xiao-Bo;Needleman, Leigh A.;El-Sabeawy, Faten;McAllister, A. Kimberley
主要组织相容性复合体I类（MHCI）分子调节活性依赖的细化和可塑性。在这里，我们发现MHCI在体外和体内皮层突触的初始建立过程中也负调控其密度和功能。MHCI分子在突触发生前和突触发生过程中在皮质神经元中表达。在体外，神经元表面MHCI （sMHCI）的减少增加了谷氨酸能和氨基丁酸能突触的密度，而过表达则降低了其密度。在体内，β2m−/−小鼠在整个发育过程中突触密度更高。MHCI也负调控mEPSC，但不负调控mIPSC的振幅，并控制皮层神经元兴奋和抑制的平衡。sMHCI水平受活动调节，并且是活动负调节谷氨酸突触密度所必需的。最后，sMHCI和活动的急性改变仅在出生后发育早期改变突触密度。这些结果确定了免疫蛋白在负调节皮层连接的初始建立和功能方面的新功能。
Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. Here, we show 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 in cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increases glutamatergic and GABAergic synapse density, while overexpression decreases it. In vivo, synapse density is higher throughout development in β2m−/ − mice. MHCI also negatively regulates mEPSC, but not mIPSC, amplitude and controls the balance of excitation and inhibition onto cortical neurons. sMHCI levels are modulated by activity and are necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity alter synapse density exclusively in early postnatal development. These results identify a novel function for immune proteins in negatively regulating the initial establishment and function of cortical connections.
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影响因子：
56.9
作者：
Huh, GS;Boulanger, LM;Shatz, CJ
通讯作者：
Shatz, CJ
影响因子：
15.3
作者：
MADRIGAL, JA;BELICH, MP;PARHAM, P
通讯作者：
PARHAM, P
影响因子：
16.2
作者：
Datwani, Akash;McConnell, Michael J.;Kanold, Patrick O.;Micheva, Kristina D.;Busse, Brad;Shamloo, Mehrdad;Smith, Stephen J.;Shatz, Carla J.
通讯作者：
Shatz, Carla J.
影响因子：
4.3
作者：
DEMARIA, S;SCHWAB, R;BUSHKIN, Y
通讯作者：
BUSHKIN, Y
影响因子：
14.8
作者：
Glynn, Marian W.;McAllister, A. Kimberley
通讯作者：
McAllister, A. Kimberley